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  • Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G
    Nat. Microbiol. Pub Date : 2017-11-20
    Darja Pollpeter, Maddy Parsons, Andrew E. Sobala, Sashika Coxhead, Rupert D. Lang, Annie M. Bruns, Stelios Papaioannou, James M. McDonnell, Luis Apolonia, Jamil A. Chowdhury, Curt M. Horvath, Michael H. Malim

    Following cell entry, the RNA genome of HIV-1 is reverse transcribed into double-stranded DNA that ultimately integrates into the host-cell genome to establish the provirus. These early phases of infection are notably vulnerable to suppression by a collection of cellular antiviral effectors, called restriction or resistance factors. The host antiviral protein APOBEC3G (A3G) antagonizes the early steps of HIV-1 infection through the combined effects of inhibiting viral cDNA production and cytidine-to-uridine-driven hypermutation of this cDNA. In seeking to address the underlying molecular mechanism for inhibited cDNA synthesis, we developed a deep sequencing strategy to characterize nascent reverse transcription products and their precise 3′-termini in HIV-1 infected T cells. Our results demonstrate site- and sequence-independent interference with reverse transcription, which requires the specific interaction of A3G with reverse transcriptase itself. This approach also established, contrary to current ideas, that cellular uracil base excision repair (UBER) enzymes target and cleave A3G-edited uridine-containing viral cDNA. Together, these findings yield further insights into the regulatory interplay between reverse transcriptase, A3G and cellular DNA repair machinery, and identify the suppression of HIV-1 reverse transcriptase by a directly interacting host protein as a new cell-mediated antiviral mechanism.

    更新日期:2017-11-21
  • Detecting macroecological patterns in bacterial communities across independent studies of global soils
    Nat. Microbiol. Pub Date : 2017-11-20
    Kelly S. Ramirez, Christopher G. Knight, Mattias de Hollander, Francis Q. Brearley, Bede Constantinides, Anne Cotton, Si Creer, Thomas W. Crowther, John Davison, Manuel Delgado-Baquerizo, Ellen Dorrepaal, David R. Elliott, Graeme Fox, Robert I. Griffiths, Chris Hale, Kyle Hartman, Ashley Houlden, David L. Jones, Eveline J. Krab, Fernando T. Maestre, Krista L. McGuire, Sylvain Monteux, Caroline H. Orr, Wim H. van der Putten, Ian S. Roberts, David A. Robinson, Jennifer D. Rocca, Jennifer Rowntree, Klaus Schlaeppi, Matthew Shepherd, Brajesh K. Singh, Angela L. Straathof, Jennifer M. Bhatnagar, Cécile Thion, Marcel G. A. van der Heijden, Franciska T. de Vries

    The emergence of high-throughput DNA sequencing methods provides unprecedented opportunities to further unravel bacterial biodiversity and its worldwide role from human health to ecosystem functioning. However, despite the abundance of sequencing studies, combining data from multiple individual studies to address macroecological questions of bacterial diversity remains methodically challenging and plagued with biases. Here, using a machine-learning approach that accounts for differences among studies and complex interactions among taxa, we merge 30 independent bacterial data sets comprising 1,998 soil samples from 21 countries. Whereas previous meta-analysis efforts have focused on bacterial diversity measures or abundances of major taxa, we show that disparate amplicon sequence data can be combined at the taxonomy-based level to assess bacterial community structure. We find that rarer taxa are more important for structuring soil communities than abundant taxa, and that these rarer taxa are better predictors of community structure than environmental factors, which are often confounded across studies. We conclude that combining data from independent studies can be used to explore bacterial community dynamics, identify potential ‘indicator’ taxa with an important role in structuring communities, and propose hypotheses on the factors that shape bacterial biogeography that have been overlooked in the past.

    更新日期:2017-11-21
  • Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice
    Nat. Microbiol. Pub Date : 2017-11-20
    Kellie A. Jurado, Laura J. Yockey, Patrick W. Wong, Sarah Lee, Anita J. Huttner, Akiko Iwasaki

    Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly1 and Guillain–Barré syndrome2,3 as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis4, meningoencephalitis5 and fatal encephalitis6. Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1−/−) mice, an infection model that exhibits high viral burden within the central nervous system. We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1 deficiency in the haematopoietic compartment. However, spread of ZIKV within the central nervous system is supported by Ifnar1-deficient non-haematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood–brain barrier and a large influx of CD8+ effector T cells. We also find that antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but, as a consequence, instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV neuropathogenesis within a susceptible mouse model and suggests blood–brain barrier breakdown and T-cell-mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.

    更新日期:2017-11-21
  • Pseudomonas aeruginosa defends against phages through type IV pilus glycosylation
    Nat. Microbiol. Pub Date : 2017-11-13
    Hanjeong Harvey, Joseph Bondy-Denomy, Hélène Marquis, Kristina M. Sztanko, Alan R. Davidson, Lori L. Burrows

    Since phages present a major challenge to survival in most environments, bacteria express a battery of anti-phage defences including CRISPR–Cas, restriction-modification and abortive infection systems1,2,3,4. Such strategies are effective, but the phage genome—which encodes potentially inhibitory gene products—is still allowed to enter the cell. The safest way to preclude phage infection is to block initial phage adsorption to the cell. Here, we describe a cell-surface modification that blocks infection by certain phages. Strains of the opportunistic pathogen Pseudomonas aeruginosa express one of five different type IV pilins (T4P)5, two of which are glycosylated with O-antigen units6 or polymers of d-arabinofuranose7,8,9. We propose that predation by bacteriophages that use T4P as receptors selects for strains that mask potential phage binding sites using glycosylation. Here, we show that both modifications protect P. aeruginosa from certain pilus-specific phages. Alterations to pilin sequence can also block phage infection, but glycosylation is considered less likely to create disadvantageous phenotypes. Through construction of chimeric phages, we show that specific phage tail proteins allow for infection of strains with glycosylated pili. These studies provide insight into first-line bacterial defences against predation and ways in which phages circumvent them, and provide a rationale for the prevalence of pilus glycosylation in nature.

    更新日期:2017-11-13
  • EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans
    Nat. Microbiol. Pub Date : 2017-11-13
    Marc Swidergall, Norma V. Solis, Michail S. Lionakis, Scott G. Filler

    Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogen Candida albicans. Binding of C. albicans to EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 and mitogen-activated protein kinase signalling in an inoculum-dependent manner, and is required for induction of a proinflammatory and antifungal response. EphA2–/– mice have impaired inflammatory responses and reduced interleukin-17 signalling during oropharyngeal candidiasis, resulting in more severe disease. Our study reveals that EphA2 functions as a PRR for β-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response to C. albicans.

    更新日期:2017-11-13
  • Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut
    Nat. Microbiol. Pub Date : 2017-11-13
    Natalya Yutin, Kira S. Makarova, Ayal B. Gussow, Mart Krupovic, Anca Segall, Robert A. Edwards, Eugene V. Koonin

    Metagenomic sequence analysis is rapidly becoming the primary source of virus discovery1,2,3. A substantial majority of the currently available virus genomes come from metagenomics, and some of these represent extremely abundant viruses, even if never grown in the laboratory. A particularly striking case of a virus discovered via metagenomics is crAssphage, which is by far the most abundant human-associated virus known, comprising up to 90% of sequences in the gut virome4. Over 80% of the predicted proteins encoded in the approximately 100 kilobase crAssphage genome showed no significant similarity to available protein sequences, precluding classification of this virus and hampering further study. Here we combine a comprehensive search of genomic and metagenomic databases with sensitive methods for protein sequence analysis to identify an expansive, diverse group of bacteriophages related to crAssphage and predict the functions of the majority of phage proteins, in particular those that comprise the structural, replication and expression modules. Most, if not all, of the crAss-like phages appear to be associated with diverse bacteria from the phylum Bacteroidetes, which includes some of the most abundant bacteria in the human gut microbiome and that are also common in various other habitats. These findings provide for experimental characterization of the most abundant but poorly understood members of the human-associated virome.

    更新日期:2017-11-13
  • Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy in hepatocytes
    Nat. Microbiol. Pub Date : 2017-11-06
    Eliana Real, Lénia Rodrigues, Ghislain G. Cabal, Francisco J. Enguita, Liliana Mancio-Silva, João Mello-Vieira, Wandy Beatty, Iset M. Vera, Vanessa Zuzarte-Luís, Tiago N. Figueira, Gunnar R. Mair, Maria M. Mota

    The causative agent of malaria, Plasmodium, replicates inside a membrane-bound parasitophorous vacuole (PV), which shields this intracellular parasite from the cytosol of the host cell1. One common threat for intracellular pathogens is the homeostatic process of autophagy, through which cells capture unwanted intracellular material for lysosomal degradation2. During the liver stage of a malaria infection, Plasmodium parasites are targeted by the autophagy machinery of the host cell, and the PV membrane (PVM) becomes decorated with several autophagy markers, including LC3 (microtubule-associated protein 1 light chain 3)3,4. Here we show that Plasmodium berghei parasites infecting hepatic cells rely on the PVM transmembrane protein UIS3 to avoid elimination by host-cell-mediated autophagy. We found that UIS3 binds host LC3 through a non-canonical interaction with a specialized surface on LC3 where host proteins with essential functions during autophagy also bind. UIS3 acts as a bona fide autophagy inhibitor by competing with host LC3-interacting proteins for LC3 binding. Our work identifies UIS3, one of the most promising candidates for a genetically attenuated vaccine against malaria5, as a unique and potent mediator of autophagy evasion in Plasmodium. We propose that the protein–protein interaction between UIS3 and host LC3 represents a target for antimalarial drug development.

    更新日期:2017-11-06
  • A bacterial pioneer produces cellulase complexes that persist through community succession
    Nat. Microbiol. Pub Date : 2017-11-06
    Sebastian Kolinko, Yu-Wei Wu, Firehiwot Tachea, Evelyn Denzel, Jennifer Hiras, Raphael Gabriel, Nora Bäcker, Leanne Jade G. Chan, Stephanie A. Eichorst, Dario Frey, Qiushi Chen, Parastoo Azadi, Paul D. Adams, Todd R. Pray, Deepti Tanjore, Christopher J. Petzold, John M. Gladden, Blake A. Simmons, Steven W. Singer

    Cultivation of microbial consortia provides low-complexity communities that can serve as tractable models to understand community dynamics. Time-resolved metagenomics demonstrated that an aerobic cellulolytic consortium cultivated from compost exhibited community dynamics consistent with the definition of an endogenous heterotrophic succession. The genome of the proposed pioneer population, ‘Candidatus Reconcilibacillus cellulovorans’, possessed a gene cluster containing multidomain glycoside hydrolases (GHs). Purification of the soluble cellulase activity from a 300litre cultivation of this consortium revealed that ~70% of the activity arose from the ‘Ca. Reconcilibacillus cellulovorans’ multidomain GHs assembled into cellulase complexes through glycosylation. These remarkably stable complexes have supramolecular structures for enzymatic cellulose hydrolysis that are distinct from cellulosomes. The persistence of these complexes during cultivation indicates that they may be active through multiple cultivations of this consortium and act as public goods that sustain the community. The provision of extracellular GHs as public goods may influence microbial community dynamics in native biomass-deconstructing communities relevant to agriculture, human health and biotechnology.

    更新日期:2017-11-06
  • Viral and cellular N6-methyladenosine and N6,2′-O-dimethyladenosine epitranscriptomes in the KSHV life cycle
    Nat. Microbiol. Pub Date : 2017-11-06
    Brandon Tan, Hui Liu, Songyao Zhang, Suzane Ramos da Silva, Lin Zhang, Jia Meng, Xiaodong Cui, Hongfeng Yuan, Océane Sorel, Shao-Wu Zhang, Yufei Huang, Shou-Jiang Gao

    Viral and cellular N6-methyladenosine and N6,2′-O-dimethyladenosine epitranscriptomes in the KSHV life cycleViral and cellular N<sup>6</sup>-methyladenosine and N<sup>6</sup>,2′-<i>O</i>-dimethyladenosine epitranscriptomes in the KSHV life cycle, Published online: 06 November 2017; doi:10.1038/s41564-017-0056-8NatureArticleSnippet(type=short-summary, markup=This study reports the viral and cellular N 6-methyladenosine (m6A) and N 6,2′-O-dimethyladenosine (m6Am) epitranscriptomes during KSHV latent and lytic infection, and shows that lytic replication induces dynamic epitranscriptome reprogramming of host pathways that control this process., isJats=true)

    更新日期:2017-11-06
  • The major targets of acute norovirus infection are immune cells in the gut-associated lymphoid tissue
    Nat. Microbiol. Pub Date : 2017-11-06
    Katrina R. Grau, Alexa N. Roth, Shu Zhu, Abel Hernandez, Natacha Colliou, Bayli B. DiVita, Drake T. Philip, Cara Riffe, Benoit Giasson, Shannon M. Wallet, Mansour Mohamadzadeh, Stephanie M. Karst

    Noroviruses are the leading cause of food-borne gastroenteritis outbreaks and childhood diarrhoea globally, estimated to be responsible for 200,000 deaths in children each year1,2,3,4. Thus, reducing norovirus-associated disease is a critical priority. Development of vaccines and therapeutics has been hindered by the limited understanding of basic norovirus pathogenesis and cell tropism. While macrophages, dendritic cells, B cells and stem-cell-derived enteroids can all support infection of certain noroviruses in vitro5,6,7, efforts to define in vivo norovirus cell tropism have generated conflicting results. Some studies detected infected intestinal immune cells8,9,10,11,12, other studies detected epithelial cells13, and still others detected immune and epithelial cells14,15,16. Major limitations of these studies are that they were performed on tissue sections from immunocompromised or germ-free hosts, chronically infected hosts where the timing of infection was unknown, or following non-biologically relevant inoculation routes. Here, we report that the dominant cellular targets of a murine norovirus inoculated orally into immunocompetent mice are macrophages, dendritic cells, B cells and T cells in the gut-associated lymphoid tissue. Importantly, we also demonstrate that a norovirus can infect T cells, a previously unrecognized target, in vitro. These findings represent the most extensive analyses to date of in vivo norovirus cell tropism in orally inoculated, immunocompetent hosts at the peak of acute infection and thus they significantly advance our basic understanding of norovirus pathogenesis.

    更新日期:2017-11-06
  • Author Correction: Evolution of host adaptation in the Salmonella typhoid toxin
    Nat. Microbiol. Pub Date : 2017-11-01
    Xiang Gao, Lingquan Deng, Gabrielle Stack, Hai Yu, Xi Chen, Yuko Naito-Matsui, Ajit Varki, Jorge E. Galán

    Author Correction: Evolution of host adaptation in the Salmonella typhoid toxinAuthor Correction: Evolution of host adaptation in the <i>Salmonella</i> typhoid toxin, Published online: 01 November 2017; doi:10.1038/s41564-017-0070-x

    更新日期:2017-11-01
  • Quantification of diverse virus populations in the environment using the polony method
    Nat. Microbiol. Pub Date : 2017-10-30
    Nava Baran, Svetlana Goldin, Ilia Maidanik, Debbie Lindell

    Viruses are globally abundant and extremely diverse in their genetic make-up and in the hosts they infect. Although they influence the abundance, diversity and evolution of their hosts, current methods are inadequate for gaining a quantitative understanding of their impact on these processes. Here we report the adaptation of the solid-phase single-molecule PCR polony method for the quantification of taxonomically relevant groups of diverse viruses. Using T7-like cyanophages as our model, we found the polony method to be far superior to regular quantitative PCR methods and droplet digital PCR when degenerate primers were used to encompass the group’s diversity. This method revealed that T7-like cyanophages were highly abundant in the Red Sea in spring 2013, reaching 770,000 phages ml−1, and displaying a similar depth distribution pattern to cyanobacteria. Furthermore, the abundances of two major clades within the T7-like cyanophages differed dramatically throughout the water column: clade B phages that carry the psbA photosynthesis gene and infect either Synechococcus or Prochlorococcus were at least 20-fold more abundant than clade A phages that lack psbA and infect Synechococcus hosts. Such measurements are of paramount importance for understanding virus population dynamics and the impact of viruses on different microbial taxa and for modelling viral influence on ecosystem functioning on a global scale.

    更新日期:2017-10-30
  • Dynamic biofilm architecture confers individual and collective mechanisms of viral protection
    Nat. Microbiol. Pub Date : 2017-10-30
    Lucia Vidakovic, Praveen K. Singh, Raimo Hartmann, Carey D. Nadell, Knut Drescher

    In nature, bacteria primarily live in surface-attached, multicellular communities, termed biofilms1,2,3,4,5,6. In medical settings, biofilms cause devastating damage during chronic and acute infections; indeed, bacteria are often viewed as agents of human disease7. However, bacteria themselves suffer from diseases, most notably in the form of viral pathogens termed bacteriophages8,9,10,11,12, which are the most abundant replicating entities on Earth. Phage–biofilm encounters are undoubtedly common in the environment, but the mechanisms that determine the outcome of these encounters are unknown. Using Escherichia coli biofilms and the lytic phage T7 as models, we discovered that an amyloid fibre network of CsgA (curli polymer) protects biofilms against phage attack via two separate mechanisms. First, collective cell protection results from inhibition of phage transport into the biofilm, which we demonstrate in vivo and in vitro. Second, CsgA fibres protect cells individually by coating their surface and binding phage particles, thereby preventing their attachment to the cell exterior. These insights into biofilm–phage interactions have broad-ranging implications for the design of phage applications in biotechnology, phage therapy and the evolutionary dynamics of phages with their bacterial hosts.

    更新日期:2017-10-30
  • DISARM is a widespread bacterial defence system with broad anti-phage activities
    Nat. Microbiol. Pub Date : 2017-10-30
    Gal Ofir, Sarah Melamed, Hila Sberro, Zohar Mukamel, Shahar Silverman, Gilad Yaakov, Shany Doron, Rotem Sorek

    The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction–modification and CRISPR–Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction–modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction–modification systems. Our results suggest that DISARM is a new type of multi-gene restriction–modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.

    更新日期:2017-10-30
  • Finding life’s missing pieces
    Nat. Microbiol. Pub Date : 2017-10-25
    Lindsey M. Solden, Kelly C. Wrighton

    Finding life’s missing pieces Nature Microbiology, Published online: 25 October 2017; doi:10.1038/s41564-017-0048-8 The Uncultivated Bacteria and Archaea dataset is a foundational collection of 7,903 genomes from uncultivated microorganisms. It highlights how microbial diversity is readily recovered using current tools and existing metagenomic datasets to help piece together the tree of life.

    更新日期:2017-10-30
  • Reduction in cholera deaths targeted for 2030
    Nat. Microbiol. Pub Date : 2017-10-25

    Reduction in cholera deaths targeted for 2030 Nature Microbiology, Published online: 25 October 2017; doi:10.1038/s41564-017-0055-9 An increased focus on identifying disease hotspots and pre-emptive intervention will be key to halting outbreaks before they become established, but political and economic obstacles cannot be ignored if ambitious new targets to reduce global cholera mortality tenfold are to be achieved.

    更新日期:2017-10-30
  • Zika virus targets blood monocytes
    Nat. Microbiol. Pub Date : 2017-10-25
    Kellie Ann Jurado, Akiko Iwasaki

    Zika virus targets blood monocytes Nature Microbiology, Published online: 25 October 2017; doi:10.1038/s41564-017-0049-7 Two studies identify circulating monocytes as the primary cellular target of Zika virus infection in human blood. Monocytes are an ideal target as they have the potential to be used as a Trojan horse to infiltrate immune-sheltered tissues, including placenta, testes and the brain, to spread Zika virus.

    更新日期:2017-10-30
  • A CRISPR–Cas9-based gene drive platform for genetic interaction analysis in Candida albicans
    Nat. Microbiol. Pub Date : 2017-10-23
    Rebecca S. Shapiro, Alejandro Chavez, Caroline B. M. Porter, Meagan Hamblin, Christian S. Kaas, James E. DiCarlo, Guisheng Zeng, Xiaoli Xu, Alexey V. Revtovich, Natalia V. Kirienko, Yue Wang, George M. Church, James J. Collins

    Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR–Cas9-based ‘gene drive array’ platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants. We generate double-gene deletion libraries to demonstrate this technology, targeting antifungal efflux and biofilm adhesion factors. We screen these libraries to identify virulence regulators and determine how genetic networks shift under diverse conditions. This platform transforms our ability to perform genetic interaction analysis in C. albicans and is readily extended to other fungal pathogens.

    更新日期:2017-10-30
  • Predicted microbial secretomes and their target substrates in marine sediment
    Nat. Microbiol. Pub Date : 2017-10-23
    William D. Orsi, Thomas A. Richards, Warren R. Francis

    Scientific drilling has identified a biosphere in marine sediments1, which contain many uncultivated microbial groups known only by their DNA sequences2,3,4. Recycling of organic matter in sediments is an important component of biogeochemical cycles because marine sediments are critical for long-term carbon storage5. Turnover of carbon is hypothesized to be driven by the secretion of enzymes by microbial organisms5,6,7, which act to break down macromolecules into constitutive monomers that can be transported into cells. As such, the nature of the microbial secretome often influences the function of a community6. However, the microbial groups involved in this process and the biochemistry they encode is poorly understood. Here, we show that expressed genes from 5 to 159 meters below the seafloor8 (mbsf) encode numerous candidate peptidases and carbohydrate-active enzymes (‘CAZymes’)9 targeted for secretion. The majority (90–99%) were assigned to Bacteria, of which 12% shared the highest sequence similarity with candidate phyla10,11. The remaining putatively secreted proteins shared highest sequence similarity with archaeal and fungal enzymes, which peak in two redox transition zones12. In the shallower redox zone at 30 mbsf, 20% of the transcripts encoding putative secreted peptidases were assigned to lineages7,13,14 of uncultivated Archaea. The target compounds of the predicted secreted proteome show a preference for necromass in the form of microbial cell envelopes as well as plankton and algal detritus. The predicted fungal secreted proteome encodes CAZymes not present in the predicted bacterial or archaeal secreted proteomes, indicating that fungi putatively play a minimal but specialized role in subseafloor carbohydrate recycling.

    更新日期:2017-10-30
  • Author Correction: Surface properties of SAR11 bacteria facilitate grazing avoidance
    Nat. Microbiol. Pub Date : 2017-10-20
    Ayelet Dadon-Pilosof, Keats R. Conley, Yuval Jacobi, Markus Haber, Fabien Lombard, Kelly R. Sutherland, Laura Steindler, Yaron Tikochinski, Michael Richter, Frank Oliver Glöckner, Marcelino T. Suzuki, Nyree J. West, Amatzia Genin, Gitai Yahel

    Author Correction: Surface properties of SAR11 bacteria facilitate grazing avoidanceNature Microbiology, Published online: 20 October 2017; doi:10.1038/s41564-017-0064-8

    更新日期:2017-10-20
  • Structural basis for maintenance of bacterial outer membrane lipid asymmetry
    Nat. Microbiol. Pub Date : 2017-10-16
    Javier Abellón-Ruiz, Shreyas S. Kaptan, Arnaud Baslé, Beatrice Claudi, Dirk Bumann, Ulrich Kleinekathöfer, Bert van den Berg

    The Gram-negative bacterial outer membrane (OM) is a unique bilayer that forms an efficient permeation barrier to protect the cell from noxious compounds1,2. The defining characteristic of the OM is lipid asymmetry, with phospholipids comprising the inner leaflet and lipopolysaccharides comprising the outer leaflet1,2,3. This asymmetry is maintained by the Mla pathway, a six-component system that is widespread in Gram-negative bacteria and is thought to mediate retrograde transport of misplaced phospholipids from the outer leaflet of the OM to the cytoplasmic membrane4. The OM lipoprotein MlaA performs the first step in this process via an unknown mechanism that does not require external energy input. Here we show, using X-ray crystallography, molecular dynamics simulations and in vitro and in vivo functional assays, that MlaA is a monomeric α-helical OM protein that functions as a phospholipid translocation channel, forming a ~20-Å-thick doughnut embedded in the inner leaflet of the OM with a central, amphipathic pore. This architecture prevents access of inner leaflet phospholipids to the pore, but allows outer leaflet phospholipids to bind to a pronounced ridge surrounding the channel, followed by diffusion towards the periplasmic space. Enterobacterial MlaA proteins form stable complexes with OmpF/C5,6, but the porins do not appear to play an active role in phospholipid transport. MlaA represents a lipid transport protein that selectively removes outer leaflet phospholipids to help maintain the essential barrier function of the bacterial OM.

    更新日期:2017-10-16
  • Self-sensing in Bacillus subtilis quorum-sensing systems
    Nat. Microbiol. Pub Date : 2017-10-16
    Tasneem Bareia, Shaul Pollak, Avigdor Eldar

    Bacterial cell–cell signalling, or quorum sensing, is characterized by the secretion and groupwide detection of small diffusible signal molecules called autoinducers. This mechanism allows cells to coordinate their behaviour in a density-dependent manner. A quorum-sensing cell may directly respond to the autoinducers it produces in a cell-autonomous and quorum-independent manner, but the strength of this self-sensing effect and its impact on bacterial physiology are unclear. Here, we explore the existence and impact of self-sensing in the Bacillus subtilis ComQXP and Rap-Phr quorum-sensing systems. By comparing the quorum-sensing response of autoinducer-secreting and non-secreting cells in co-culture, we find that secreting cells consistently show a stronger response than non-secreting cells. Combining genetic and quantitative analyses, we demonstrate this effect to be a direct result of self-sensing and rule out an indirect regulatory effect of the autoinducer production genes on response sensitivity. In addition, self-sensing in the ComQXP system affects persistence to antibiotic treatment. Together, these findings indicate the existence of self-sensing in the two most common designs of quorum-sensing systems of Gram-positive bacteria.

    更新日期:2017-10-16
  • Evolution of host adaptation in the Salmonella typhoid toxin
    Nat. Microbiol. Pub Date : 2017-10-09
    Xiang Gao, Lingquan Deng, Gabrielle Stack, Hai Yu, Xi Chen, Yuko Naito-Matsui, Ajit Varki, Jorge E. Galán

    The evolution of virulence traits is central for the emergence or re-emergence of microbial pathogens and for their adaptation to a specific host1,2,3,4,5. Typhoid toxin is an essential virulence factor of the human-adapted bacterial pathogen Salmonella Typhi6,7, the cause of typhoid fever in humans8,9,10,11,12. Typhoid toxin has a unique A2B5 architecture with two covalently linked enzymatic ‘A’ subunits, PltA and CdtB, associated with a homopentameric ‘B’ subunit made up of PltB, which has binding specificity for the N-acetylneuraminic acid (Neu5Ac) sialoglycans6,13 predominantly present in humans14. Here, we examine the functional and structural relationship between typhoid toxin and ArtAB, an evolutionarily related AB5 toxin encoded by the broad-host Salmonella Typhimurium15. We find that ArtA and ArtB, homologues of PltA and PltB, can form a functional complex with the typhoid toxin CdtB subunit after substitution of a single amino acid in ArtA, while ArtB can form a functional complex with wild-type PltA and CdtB. We also found that, after addition of a single-terminal Cys residue, a CdtB homologue from cytolethal distending toxin can form a functional complex with ArtA and ArtB. In line with the broad host specificity of S. Typhimurium, we found that ArtB binds human glycans, terminated in N-acetylneuraminic acid, as well as glycans terminated in N-glycolylneuraminic acid (Neu5Gc), which are expressed in most other mammals14. The atomic structure of ArtB bound to its receptor shows the presence of an additional glycan-binding site, which broadens its binding specificity. Despite equivalent toxicity in vitro, we found that the ArtB/PltA/CdtB chimaeric toxin exhibits reduced lethality in an animal model, indicating that the host specialization of typhoid toxin has optimized its targeting mechanisms to the human host. This is a remarkable example of a toxin evolving to broaden its enzymatic activities and adapt to a specific host.

    更新日期:2017-10-11
  • Natural product diversity associated with the nematode symbionts Photorhabdus and Xenorhabdus
    Nat. Microbiol. Pub Date : 2017-10-09
    Nicholas J. Tobias, Hendrik Wolff, Bardya Djahanschiri, Florian Grundmann, Max Kronenwerth, Yi-Ming Shi, Svenja Simonyi, Peter Grün, David Shapiro-Ilan, Sacha J. Pidot, Timothy P. Stinear, Ingo Ebersberger, Helge B. Bode

    Xenorhabdus and Photorhabdus species dedicate a large amount of resources to the production of specialized metabolites derived from non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS). Both bacteria undergo symbiosis with nematodes, which is followed by an insect pathogenic phase. So far, the molecular basis of this tripartite relationship and the exact roles that individual metabolites and metabolic pathways play have not been well understood. To close this gap, we have significantly expanded the database for comparative genomics studies in these bacteria. Clustering the genes encoded in the individual genomes into hierarchical orthologous groups reveals a high-resolution picture of functional evolution in this clade. It identifies groups of genes—many of which are involved in secondary metabolite production—that may account for the niche specificity of these bacteria. Photorhabdus and Xenorhabdus appear very similar at the DNA sequence level, which indicates their close evolutionary relationship. Yet, high-resolution mass spectrometry analyses reveal a huge chemical diversity in the two taxa. Molecular network reconstruction identified a large number of previously unidentified metabolite classes, including the xefoampeptides and tilivalline. Here, we apply genomic and metabolomic methods in a complementary manner to identify and elucidate additional classes of natural products. We also highlight the ability to rapidly and simultaneously identify potentially interesting bioactive products from NRPSs and PKSs, thereby augmenting the contribution of molecular biology techniques to the acceleration of natural product discovery.

    更新日期:2017-10-11
  • D-Alanylation of teichoic acids contributes to Lactobacillus plantarum-mediated Drosophila growth during chronic undernutrition
    Nat. Microbiol. Pub Date : 2017-10-09
    Renata C. Matos, Martin Schwarzer, Hugo Gervais, Pascal Courtin, Pauline Joncour, Benjamin Gillet, Dali Ma, Anne-Laure Bulteau, Maria Elena Martino, Sandrine Hughes, Marie-Pierre Chapot-Chartier, François Leulier

    The microbial environment influences animal physiology. However, the underlying molecular mechanisms of such functional interactions are largely undefined. Previously, we showed that during chronic undernutrition, strains of Lactobacillus plantarum, a major commensal partner of Drosophila, promote host juvenile growth and maturation partly through enhanced expression of intestinal peptidases. By screening a transposon insertion library of Lactobacillus plantarum in gnotobiotic Drosophila larvae, we identify a bacterial cell-wall-modifying machinery encoded by the pbpX2-dlt operon that is critical to enhance host digestive capabilities and promote animal growth and maturation. Deletion of this operon leads to bacterial cell wall alteration with a complete loss of d-alanylation of teichoic acids. We show that L. plantarum cell walls bearing d-alanylated teichoic acids are directly sensed by Drosophila enterocytes to ensure optimal intestinal peptidase expression and activity, juvenile growth and maturation during chronic undernutrition. We thus conclude that besides peptidoglycan, teichoic acid modifications participate in the host–commensal bacteria molecular dialogue occurring in the intestine.

    更新日期:2017-10-11
  • Structure of the calcium-dependent type 2 secretion pseudopilus
    Nat. Microbiol. Pub Date : 2017-10-09
    Aracelys López-Castilla, Jenny-Lee Thomassin, Benjamin Bardiaux, Weili Zheng, Mangayarkarasi Nivaskumar, Xiong Yu, Michael Nilges, Edward H. Egelman, Nadia Izadi-Pruneyre, Olivera Francetic

    Many Gram-negative bacteria use type 2 secretion systems (T2SSs) to secrete proteins involved in virulence and adaptation. Transport of folded proteins via T2SS nanomachines requires the assembly of inner membrane-anchored fibres called pseudopili. Although efficient pseudopilus assembly is essential for protein secretion, structure-based functional analyses are required to unravel the mechanistic link between these processes. Here, we report an atomic model for a T2SS pseudopilus from Klebsiella oxytoca, obtained by fitting the NMR structure of its calcium-bound subunit PulG into the ~5-Å-resolution cryo-electron microscopy reconstruction of assembled fibres. This structure reveals the comprehensive network of inter-subunit contacts and unexpected features, including a disordered central region of the PulG helical stem, and highly flexible C-terminal residues on the fibre surface. NMR, mutagenesis and functional analyses highlight the key role of calcium in PulG folding and stability. Fibre disassembly in the absence of calcium provides a basis for pseudopilus length control, essential for protein secretion, and supports the Archimedes screw model for the type 2 secretion mechanism.

    更新日期:2017-10-11
  • Fluorescent D-amino-acids reveal bi-cellular cell wall modifications important for Bdellovibrio bacteriovorus predation
    Nat. Microbiol. Pub Date : 2017-10-03
    Erkin Kuru, Carey Lambert, Jonathan Rittichier, Rob Till, Adrien Ducret, Adeline Derouaux, Joe Gray, Jacob Biboy, Waldemar Vollmer, Michael VanNieuwenhze, Yves V. Brun, R. Elizabeth Sockett

    Modification of essential bacterial peptidoglycan (PG)-containing cell walls can lead to antibiotic resistance; for example, β-lactam resistance by l,d-transpeptidase activities. Predatory Bdellovibrio bacteriovorus are naturally antibacterial and combat infections by traversing, modifying and finally destroying walls of Gram-negative prey bacteria, modifying their own PG as they grow inside prey. Historically, these multi-enzymatic processes on two similar PG walls have proved challenging to elucidate. Here, with a PG-labelling approach utilizing timed pulses of multiple fluorescent d-amino acids, we illuminate dynamic changes that predator and prey walls go through during the different phases of bacteria:bacteria invasion. We show formation of a reinforced circular port-hole in the prey wall, l,d-transpeptidaseBd-mediated d-amino acid modifications strengthening prey PG during Bdellovibrio invasion, and a zonal mode of predator elongation. This process is followed by unconventional, multi-point and synchronous septation of the intracellular Bdellovibrio, accommodating odd- and even-numbered progeny formation by non-binary division.

    更新日期:2017-10-11
  • Author Correction: Re-examination of the relationship between marine virus and microbial cell abundances
    Nat. Microbiol. Pub Date : 2017-10-03
    Charles H. Wigington, Derek Sonderegger, Corina P. D. Brussaard, Alison Buchan, Jan F. Finke, Jed A. Fuhrman, Jay T. Lennon, Mathias Middelboe, Curtis A. Suttle, Charles Stock, William H. Wilson, K. Eric Wommack, Steven W. Wilhelm, Joshua S. Weitz

    Author Correction: Re-examination of the relationship between marine virus and microbial cell abundances Nature Microbiology, Published online: 3 October 2017; doi:10.1038/s41564-017-0042-1

    更新日期:2017-10-11
  • Surface properties of SAR11 bacteria facilitate grazing avoidance
    Nat. Microbiol. Pub Date : 2017-10-02
    Ayelet Dadon-Pilosof, Keats R. Conley, Yuval Jacobi, Markus Haber, Fabien Lombard, Kelly R. Sutherland, Laura Steindler, Yaron Tikochinski, Michael Richter, Frank Oliver Glöckner, Marcelino T. Suzuki, Nyree J. West, Amatzia Genin, Gitai Yahel

    Oceanic ecosystems are dominated by minute microorganisms that play a major role in food webs and biogeochemical cycles1. Many microorganisms thrive in the dilute environment due to their capacity to locate, attach to, and use patches of nutrients and organic matter2,3. We propose that some free-living planktonic bacteria have traded their ability to stick to nutrient-rich organic particles for a non-stick cell surface that helps them evade predation by mucous filter feeders. We used a combination of in situ sampling techniques and next-generation sequencing to study the biological filtration of microorganisms at the phylotype level. Our data indicate that some marine bacteria, most notably the highly abundant Pelagibacter ubique and most other members of the SAR 11 clade of the Alphaproteobacteria, can evade filtration by slipping through the mucous nets of both pelagic and benthic tunicates. While 0.3 µm polystyrene beads and other similarly-sized bacteria were efficiently filtered, SAR11 members were not captured. Reversed-phase chromatography revealed that most SAR11 bacteria have a much less hydrophobic cell surface than that of other planktonic bacteria. Our data call for a reconsideration of the role of surface properties in biological filtration and predator-prey interactions in aquatic systems.

    更新日期:2017-10-11
  • Contribution of reactive oxygen species to thymineless death in Escherichia coli
    Nat. Microbiol. Pub Date : 2017-10-02
    Yuzhi Hong, Liping Li, Gan Luan, Karl Drlica, Xilin Zhao

    Nutrient starvation usually halts cell growth rather than causing death. Thymine starvation is exceptional, because it kills cells rapidly. This phenomenon, called thymineless death (TLD), underlies the action of several antibacterial, antimalarial, anticancer, and immunomodulatory agents. Many explanations for TLD have been advanced, with recent efforts focused on recombination proteins and replication origin (oriC) degradation. Because current proposals account for only part of TLD and because reactive oxygen species (ROS) are implicated in bacterial death due to other forms of harsh stress, we investigated the possible involvement of ROS in TLD. Here, we show that thymine starvation leads to accumulation of both single-stranded DNA regions and intracellular ROS, and interference with either event protects bacteria from double-stranded DNA breakage and TLD. Elevated levels of single-stranded DNA were necessary but insufficient for TLD, whereas reduction of ROS to background levels largely abolished TLD. We conclude that ROS contribute to TLD by converting single-stranded DNA lesions into double-stranded DNA breaks. Participation of ROS in the terminal phases of TLD provides a specific example of how ROS contribute to stress-mediated bacterial self-destruction.

    更新日期:2017-10-11
  • Cheese, phages and anti-CRISPRs
    Nat. Microbiol. Pub Date : 2017-09-26
    Alan R. Davidson

    Cheese, phages and anti-CRISPRs Nature Microbiology, Published online: 26 September 2017; doi:10.1038/s41564-017-0026-1 The study of phages that pose a threat to the cheese industry, which enabled the original demonstration that CRISPR–Cas systems work as adaptive immune systems in bacteria, now leads to the identification of a new anti-CRISPR that inhibits Cas9 from Streptococcus pyogenes.

    更新日期:2017-09-26
  • Better support translational research
    Nat. Microbiol. Pub Date : 2017-09-26

    Better support translational research Nature Microbiology, Published online: 26 September 2017; doi:10.1038/s41564-017-0040-3 Translating scientific discoveries into real world solutions is a goal shared by researchers, governments, industry and the public alike. While continued support for basic research is critical, improvements in the funding, evaluation and publication of translational work are also needed to fully realize the promise of applied research.

    更新日期:2017-09-26
  • Streptococci target inflammasome
    Nat. Microbiol. Pub Date : 2017-09-26
    Madeleine W. Cunningham

    Streptococci target inflammasome Nature Microbiology, Published online: 26 September 2017; doi:10.1038/s41564-017-0031-4 The Streptococcus pyogenes surface M protein is a critical multifunctional virulence factor. Recent work sheds light on a new unexpected function of the M protein in activating the host inflammasome to induce macrophage cell death and promote infection.

    更新日期:2017-09-26
  • Hitting malaria where it hurts
    Nat. Microbiol. Pub Date : 2017-09-26
    Thierry Diagana, Catherine Jones

    Hitting malaria where it hurts Nature Microbiology, Published online: 26 September 2017; doi:10.1038/s41564-017-0036-z The goal of malaria eradication is threatened by drug resistance. Now, two studies characterize Plasmodium falciparum PKG inhibitors and hexahydroquinolines as antimalarial compounds that could block transmission and help mitigate the risk of parasite escape via drug resistance.

    更新日期:2017-09-26
  • New options to treat influenza B
    Nat. Microbiol. Pub Date : 2017-09-26
    Aeron C. Hurt, Kanta Subbarao

    New options to treat influenza B Nature Microbiology, Published online: 26 September 2017; doi:10.1038/s41564-017-0027-0 Influenza B virus causes substantial illness globally, particularly in children. Treatment options are limited, as the most widely used antiviral drug appears to be less effective than against influenza A. A new antibody targeting the influenza B neuraminidase shows promise in mice as a therapeutic option.

    更新日期:2017-09-26
  • Plasmid vesicles mimicking virions
    Nat. Microbiol. Pub Date : 2017-09-26
    Patrick Forterre, Violette Da Cunha, Ryan Catchpole

    Plasmid vesicles mimicking virions Nature Microbiology, Published online: 26 September 2017; doi:10.1038/s41564-017-0032-3 A newly described plasmid, which encodes proteins facilitating its packaging and cell-to-cell transfer via membrane vesicles, challenges the way we think about the delineation of viruses, plasmids and extracellular vesicles.

    更新日期:2017-09-26
  • A metabolic pathway for catabolizing levulinic acid in bacteria
    Nat. Microbiol. Pub Date : 2017-09-25
    Jacqueline M. Rand, Tippapha Pisithkul, Ryan L. Clark, Joshua M. Thiede, Christopher R. Mehrer, Daniel E. Agnew, Candace E. Campbell, Andrew L. Markley, Morgan N. Price, Jayashree Ray, Kelly M. Wetmore, Yumi Suh, Adam P. Arkin, Adam M. Deutschbauer, Daniel Amador-Noguez, Brian F. Pfleger

    Microorganisms can catabolize a wide range of organic compounds and therefore have the potential to perform many industrially relevant bioconversions. One barrier to realizing the potential of biorefining strategies lies in our incomplete knowledge of metabolic pathways, including those that can be used to assimilate naturally abundant or easily generated feedstocks. For instance, levulinic acid (LA) is a carbon source that is readily obtainable as a dehydration product of lignocellulosic biomass and can serve as the sole carbon source for some bacteria. Yet, the genetics and structure of LA catabolism have remained unknown. Here, we report the identification and characterization of a seven-gene operon that enables LA catabolism in Pseudomonas putida KT2440. When the pathway was reconstituted with purified proteins, we observed the formation of four acyl-CoA intermediates, including a unique 4-phosphovaleryl-CoA and the previously observed 3-hydroxyvaleryl-CoA product. Using adaptive evolution, we obtained a mutant of Escherichia coli LS5218 with functional deletions of fadE and atoC that was capable of robust growth on LA when it expressed the five enzymes from the P. putida operon. This discovery will enable more efficient use of biomass hydrolysates and metabolic engineering to develop bioconversions using LA as a feedstock.

    更新日期:2017-09-25
  • An integrative circuit–host modelling framework for predicting synthetic gene network behaviours
    Nat. Microbiol. Pub Date : 2017-09-25
    Chen Liao, Andrew E. Blanchard, Ting Lu

    One fundamental challenge in synthetic biology is the lack of quantitative tools that accurately describe and predict the behaviours of engineered gene circuits. This challenge arises from multiple factors, among which the complex interdependence of circuits and their host is a leading cause. Here we present a gene circuit modelling framework that explicitly integrates circuit behaviours with host physiology through bidirectional circuit–host coupling. The framework consists of a coarse-grained but mechanistic description of host physiology that involves dynamic resource partitioning, multilayered circuit–host coupling including both generic and system-specific interactions, and a detailed kinetic module of exogenous circuits. We showed that, following training, the framework was able to capture and predict a large set of experimental data concerning the host and its foreign gene overexpression. To demonstrate its utility, we applied the framework to examine a growth-modulating feedback circuit whose dynamics is qualitatively altered by circuit–host interactions. Using an extended version of the framework, we further systematically revealed the behaviours of a toggle switch across scales from single-cell dynamics to population structure and to spatial ecology. This work advances our quantitative understanding of gene circuit behaviours and also benefits the rational design of synthetic gene networks.

    更新日期:2017-09-25
  • Dietary alterations modulate susceptibility to Plasmodium infection
    Nat. Microbiol. Pub Date : 2017-09-25
    Vanessa Zuzarte-Luís, João Mello-Vieira, Inês M. Marreiros, Peter Liehl, Ângelo F. Chora, Céline K. Carret, Tânia Carvalho, Maria M. Mota

    The relevance of genetic factors in conferring protection to severe malaria has been demonstrated, as in the case of sickle cell trait and G6PD deficiency1. However, it remains unknown whether environmental components, such as dietary or metabolic variations, can contribute to the outcome of infection2. Here, we show that administration of a high-fat diet to mice for a period as short as 4 days impairs Plasmodium liver infection by over 90%. Plasmodium sporozoites can successfully invade and initiate replication but die inside hepatocytes, thereby are unable to cause severe disease. Transcriptional analyses combined with genetic and chemical approaches reveal that this impairment of infection is mediated by oxidative stress. We show that reactive oxygen species, probably spawned from fatty acid β-oxidation, directly impact Plasmodium survival inside hepatocytes, and parasite load can be rescued by exogenous administration of the antioxidant N-acetylcysteine or the β-oxidation inhibitor etomoxir. Together, these data reveal that acute and transient dietary alterations markedly impact the establishment of a Plasmodium infection and disease outcome.

    更新日期:2017-09-25
  • Cryo-EM structure of the extended type VI secretion system sheath–tube complex
    Nat. Microbiol. Pub Date : 2017-09-25
    Jing Wang, Maximilian Brackmann, Daniel Castaño-Díez, Mikhail Kudryashev, Kenneth N. Goldie, Timm Maier, Henning Stahlberg, Marek Basler

    The bacterial type VI secretion system (T6SS) uses contraction of a long sheath to quickly thrust a tube with associated effectors across membranes of eukaryotic and bacterial cells1,2,3,4,5. Only limited structural information is available about the inherently unstable precontraction state of the T6SS. Here, we obtain a 3.7 Å resolution structure of a non-contractile sheath–tube complex using cryo-electron microscopy and show that it resembles the extended T6SS inside Vibrio cholerae cells. We build a pseudo-atomic model of the complete sheath–tube assembly, which provides a mechanistic understanding of coupling sheath contraction with pushing and rotating the inner tube for efficient target membrane penetration. Our data further show that sheath contraction exposes a buried recognition domain to specifically trigger the disassembly and recycling of the T6SS sheath by the cognate ATP-dependent unfoldase ClpV.

    更新日期:2017-09-25
  • Metabolic crosstalk regulates Porphyromonas gingivalis colonization and virulence during oral polymicrobial infection
    Nat. Microbiol. Pub Date : 2017-09-18
    Masae Kuboniwa, John R. Houser, Erik L. Hendrickson, Qian Wang, Samar A. Alghamdi, Akito Sakanaka, Daniel P. Miller, Justin A. Hutcherson, Tiansong Wang, David A. C. Beck, Marvin Whiteley, Atsuo Amano, Huizhi Wang, Edward M. Marcotte, Murray Hackett, Richard J. Lamont

    Many human infections are polymicrobial in origin, and interactions among community inhabitants shape colonization patterns and pathogenic potential1. Periodontitis, which is the sixth most prevalent infectious disease worldwide2, ensues from the action of dysbiotic polymicrobial communities3. The keystone pathogen Porphyromonas gingivalis and the accessory pathogen Streptococcus gordonii interact to form communities in vitro and exhibit increased fitness in vivo3,4. The mechanistic basis of this polymicrobial synergy, however, has not been fully elucidated. Here we show that streptococcal 4-aminobenzoate/para-amino benzoic acid (pABA) is required for maximal accumulation of P. gingivalis in dual-species communities. Metabolomic and proteomic data showed that exogenous pABA is used for folate biosynthesis, and leads to decreased stress and elevated expression of fimbrial adhesins. Moreover, pABA increased the colonization and survival of P. gingivalis in a murine oral infection model. However, pABA also caused a reduction in virulence in vivo and suppressed extracellular polysaccharide production by P. gingivalis. Collectively, these data reveal a multidimensional aspect to P. gingivalis–S. gordonii interactions and establish pABA as a critical cue produced by a partner species that enhances the fitness of P. gingivalis while diminishing its virulence.

    更新日期:2017-09-19
  • Communication via extracellular vesicles enhances viral infection of a cosmopolitan alga
    Nat. Microbiol. Pub Date : 2017-09-18
    Daniella Schatz, Shilo Rosenwasser, Sergey Malitsky, Sharon G. Wolf, Ester Feldmesser, Assaf Vardi

    Communication between microorganisms in the marine environment has immense ecological impact by mediating trophic-level interactions and thus determining community structure1. Extracellular vesicles (EVs) are produced by bacteria2,3, archaea4, protists5 and metazoans, and can mediate pathogenicity6 or act as vectors for intercellular communication. However, little is known about the involvement of EVs in microbial interactions in the marine environment7. Here we investigated the signalling role of EVs produced during interactions between the cosmopolitan alga Emiliania huxleyi and its specific virus (EhV, Phycodnaviridae)8, which leads to the demise of these large-scale oceanic blooms9,10. We found that EVs are highly produced during viral infection or when bystander cells are exposed to infochemicals derived from infected cells. These vesicles have a unique lipid composition that differs from that of viruses and their infected host cells, and their cargo is composed of specific small RNAs that are predicted to target sphingolipid metabolism and cell-cycle pathways. EVs can be internalized by E. huxleyi cells, which consequently leads to a faster viral infection dynamic. EVs can also prolong EhV half-life in the extracellular milieu. We propose that EVs are exploited by viruses to sustain efficient infectivity and propagation across E. huxleyi blooms. As these algal blooms have an immense impact on the cycling of carbon and other nutrients11,12, this mode of cell–cell communication may influence the fate of the blooms and, consequently, the composition and flow of nutrients in marine microbial food webs.

    更新日期:2017-09-19
  • APOLs with low pH dependence can kill all African trypanosomes
    Nat. Microbiol. Pub Date : 2017-09-18
    Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga, Etienne Pays

    The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins1,2,3,4. APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense3. We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes, including T.b. rhodesiense, T.b. gambiense and the animal pathogens Trypanosoma evansi, Trypanosoma congolense and Trypanosoma vivax. However, rAPOL3 did not kill more distant trypanosomes such as Trypanosoma theileri or Trypanosoma cruzi. This trypanolytic potential was partially shared by rAPOL1 from Papio papio (rPpAPOL1). The differential killing ability of rAPOL3 and rAPOL1 was associated with a distinct dependence on acidic pH for activity. Due both to its instability and toxicity when injected into mice, rAPOL3 cannot be used for the treatment of infection, but an experimental rPpAPOL1 mutant inspired by APOL3 exhibited enhanced trypanolytic activity in vitro and the ability to completely inhibit T.b. gambiense infection in mice. We conclude that pH dependence influences the trypanolytic potential of rAPOLs.

    更新日期:2017-09-19
  • Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life
    Nat. Microbiol. Pub Date : 2017-09-11
    Donovan H. Parks, Christian Rinke, Maria Chuvochina, Pierre-Alain Chaumeil, Ben J. Woodcroft, Paul N. Evans, Philip Hugenholtz, Gene W. Tyson

    Challenges in cultivating microorganisms have limited the phylogenetic diversity of currently available microbial genomes. This is being addressed by advances in sequencing throughput and computational techniques that allow for the cultivation-independent recovery of genomes from metagenomes. Here, we report the reconstruction of 7,903 bacterial and archaeal genomes from >1,500 public metagenomes. All genomes are estimated to be ≥50% complete and nearly half are ≥90% complete with ≤5% contamination. These genomes increase the phylogenetic diversity of bacterial and archaeal genome trees by >30% and provide the first representatives of 17 bacterial and three archaeal candidate phyla. We also recovered 245 genomes from the Patescibacteria superphylum (also known as the Candidate Phyla Radiation) and find that the relative diversity of this group varies substantially with different protein marker sets. The scale and quality of this data set demonstrate that recovering genomes from metagenomes provides an expedient path forward to exploring microbial dark matter.

    更新日期:2017-09-11
  • Structural basis for the shielding function of the dynamic trypanosome variant surface glycoprotein coat
    Nat. Microbiol. Pub Date : 2017-09-11
    Thomas Bartossek, Nicola G. Jones, Christin Schäfer, Mislav Cvitković, Marius Glogger, Helen R. Mott, Jochen Kuper, Martha Brennich, Mark Carrington, Ana-Sunčana Smith, Susanne Fenz, Caroline Kisker, Markus Engstler

    The most prominent defence of the unicellular parasite Trypanosoma brucei against the host immune system is a dense coat that comprises a variant surface glycoprotein (VSG). Despite the importance of the VSG family, no complete structure of a VSG has been reported. Making use of high-resolution structures of individual VSG domains, we employed small-angle X-ray scattering to elucidate the first two complete VSG structures. The resulting models imply that the linker regions confer great flexibility between domains, which suggests that VSGs can adopt two main conformations to respond to obstacles and changes of protein density, while maintaining a protective barrier at all times. Single-molecule diffusion measurements of VSG in supported lipid bilayers substantiate this possibility, as two freely diffusing populations could be detected. This translates into a highly flexible overall topology of the surface VSG coat, which displays both lateral movement in the plane of the membrane and variation in the overall thickness of the coat.

    更新日期:2017-09-11
  • A viral protein antibiotic inhibits lipid II flippase activity
    Nat. Microbiol. Pub Date : 2017-09-11
    Karthik R. Chamakura, Lok-To Sham, Rebecca M. Davis, Lorna Min, Hongbaek Cho, Natividad Ruiz, Thomas G. Bernhardt, Ry Young

    For bacteriophage infections, the cell walls of bacteria, consisting of a single highly polymeric molecule of peptidoglycan (PG), pose a major problem for the release of progeny virions. Phage lysis proteins that overcome this barrier can point the way to new antibacterial strategies1, especially small lytic single-stranded DNA (the microviruses) and RNA phages (the leviviruses) that effect host lysis using a single non-enzymatic protein2. Previously, the A2 protein of levivirus Qβ and the E protein of the microvirus ϕX174 were shown to be ‘protein antibiotics’ that inhibit the MurA and MraY steps of the PG synthesis pathway2,3,4. Here, we investigated the mechanism of action of an unrelated lysis protein, LysM, of the Escherichia coli levivirus M5. We show that LysM inhibits the translocation of the final lipid-linked PG precursor called lipid II across the cytoplasmic membrane by interfering with the activity of MurJ. The finding that LysM inhibits a distinct step in the PG synthesis pathway from the A2 and E proteins indicates that small phages, particularly the single-stranded RNA (ssRNA) leviviruses, have a previously unappreciated capacity for evolving novel inhibitors of PG biogenesis despite their limited coding potential.

    更新日期:2017-09-11
  • CD81 association with SAMHD1 enhances HIV-1 reverse transcription by increasing dNTP levels
    Nat. Microbiol. Pub Date : 2017-09-04
    Vera Rocha-Perugini, Henar Suárez, Susana Álvarez, Soraya López-Martín, Gina M. Lenzi, Felipe Vences-Catalán, Shoshana Levy, Baek Kim, María A. Muñoz-Fernández, Francisco Sánchez-Madrid, Maria Yáñez-Mó

    In this study, we report that the tetraspanin CD81 enhances human immunodeficiency virus (HIV)-1 reverse transcription in HIV-1-infected cells. This is enabled by the direct interaction of CD81 with the deoxynucleoside triphosphate phosphohydrolase SAMHD1. This interaction prevents endosomal accumulation and favours the proteasome-dependent degradation of SAMHD1. Consequently, CD81 depletion results in SAMHD1 increased expression, decreasing the availability of deoxynucleoside triphosphates (dNTP) and thus HIV-1 reverse transcription. Conversely, CD81 overexpression, but not the expression of a CD81 carboxy (C)-terminal deletion mutant, increases cellular dNTP content and HIV-1 reverse transcription. Our results demonstrate that the interaction of CD81 with SAMHD1 controls the metabolic rate of HIV-1 replication by tuning the availability of building blocks for reverse transcription, namely dNTPs. Together with its role in HIV-1 entry and budding into host cells, the data herein indicate that HIV-1 uses CD81 as a rheostat that controls different stages of the infection.

    更新日期:2017-09-04
  • Interspecies quorum sensing in co-infections can manipulate trypanosome transmission potential
    Nat. Microbiol. Pub Date : 2017-09-04
    Eleanor Silvester, Julie Young, Alasdair Ivens, Keith R. Matthews

    Quorum sensing (QS) is commonly used in microbial communities and some unicellular parasites to coordinate group behaviours1,2. An example is Trypanosoma brucei, which causes human African trypanosomiasis, as well as the livestock disease, nagana. Trypanosomes are spread by tsetse flies, their transmission being enabled by cell-cycle arrested ‘stumpy forms’ that are generated in a density-dependent manner in mammalian blood. QS is mediated through a small (<500 Da), non-proteinaceous, stable but unidentified ‘stumpy induction factor’3, whose signal response pathway has been identified. Although QS is characterized in T. brucei, co-infections with other trypanosome species (Trypanosoma congolense and Trypanosoma vivax) are common in animals, generating the potential for interspecies interactions. Here, we show that T. congolense exhibits density-dependent growth control in vivo and conserves QS regulatory genes, of which one can complement a T. brucei QS signal-blind mutant to restore stumpy formation. Thereafter, we demonstrate that T. congolense-conditioned culture medium promotes T. brucei stumpy formation in vitro, which is dependent on the integrity of the QS signalling pathway. Finally, we show that, in vivo, co-infection with T. congolense accelerates differentiation to stumpy forms in T. brucei, which is also QS dependent. These cross-species interactions have important implications for trypanosome virulence, transmission, competition and evolution in the field.

    更新日期:2017-09-04
  • TRIM23 mediates virus-induced autophagy via activation of TBK1
    Nat. Microbiol. Pub Date : 2017-09-04
    Konstantin M. J. Sparrer, Sebastian Gableske, Matthew A. Zurenski, Zachary M. Parker, Florian Full, Gavin J. Baumgart, Jiro Kato, Gustavo Pacheco-Rodriguez, Chengyu Liang, Owen Pornillos, Joel Moss, Martha Vaughan, Michaela U. Gack

    Autophagy and interferon (IFN)-mediated innate immunity are critical antiviral defence mechanisms, and recent evidence indicated that tripartite motif (TRIM) proteins are important regulators of both processes. Although the role of TRIM proteins in modulating antiviral cytokine responses has been well established, much less is known about their involvement in autophagy in response to different viral pathogens. Through a targeted RNAi screen examining the relevance of selected TRIM proteins in autophagy induced by herpes simplex virus 1 (HSV-1), encephalomyocarditis virus (EMCV) and influenza A virus (IAV), we identified several TRIM proteins that regulate autophagy in a virus-species-specific manner, as well as a few TRIM proteins that were essential for autophagy triggered by all three viruses and rapamycin, among them TRIM23. TRIM23 was critical for autophagy-mediated restriction of multiple viruses, and this activity was dependent on both its RING E3 ligase and ADP-ribosylation factor (ARF) GTPase activity. Mechanistic studies revealed that unconventional K27-linked auto-ubiquitination of the ARF domain is essential for the GTP hydrolysis activity of TRIM23 and activation of TANK-binding kinase 1 (TBK1) by facilitating its dimerization and ability to phosphorylate the selective autophagy receptor p62. Our work identifies the TRIM23-TBK1-p62 axis as a key component of selective autophagy and further reveals a role for K27-linked ubiquitination in GTPase-dependent TBK1 activation.

    更新日期:2017-09-04
  • Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation
    Nat. Microbiol. Pub Date : 2017-08-28
    Weiqiang Chen, Suan-Sin Foo, Ali Zaid, Terk-Shin Teng, Lara J. Herrero, Stefan Wolf, Kothila Tharmarajah, Luan D. Vu, Caryn van Vreden, Adam Taylor, Joseph R. Freitas, Rachel W. Li, Trent M. Woodruff, Richard Gordon, David M. Ojcius, Helder I. Nakaya, Thirumala-Devi Kanneganti, Luke A. J. O’Neill, Avril A. B. Robertson, Nicholas J. King, Andreas Suhrbier, Matthew A. Cooper, Lisa F. P. Ng, Suresh Mahalingam

    Mosquito-borne viruses can cause severe inflammatory diseases and there are limited therapeutic solutions targeted specifically at virus-induced inflammation. Chikungunya virus (CHIKV), a re-emerging alphavirus responsible for several outbreaks worldwide in the past decade, causes debilitating joint inflammation and severe pain. Here, we show that CHIKV infection activates the NLRP3 inflammasome in humans and mice. Peripheral blood mononuclear cells isolated from CHIKV-infected patients showed elevated NLRP3, caspase-1 and interleukin-18 messenger RNA expression and, using a mouse model of CHIKV infection, we found that high NLRP3 expression was associated with peak inflammatory symptoms. Inhibition of NLRP3 activation using the small-molecule inhibitor MCC950 resulted in reduced CHIKV-induced inflammation and abrogated osteoclastogenic bone loss and myositis, but did not affect in vivo viral replication. Mice treated with MCC950 displayed lower expression levels of the cytokines interleukin-6, chemokine ligand 2 and tumour necrosis factor in joint tissue. Interestingly, MCC950 treatment abrogated disease signs in mice infected with a related arthritogenic alphavirus, Ross River virus, but not in mice infected with West Nile virus—a flavivirus. Here, using mouse models of alphavirus-induced musculoskeletal disease, we demonstrate that NLRP3 inhibition in vivo can reduce inflammatory pathology and that further development of therapeutic solutions targeting inflammasome function could help treat arboviral diseases.

    更新日期:2017-08-28
  • A microfluidics-based in situ chemotaxis assay to study the behaviour of aquatic microbial communities
    Nat. Microbiol. Pub Date : 2017-08-28
    Bennett S. Lambert, Jean-Baptiste Raina, Vicente I. Fernandez, Christian Rinke, Nachshon Siboni, Francesco Rubino, Philip Hugenholtz, Gene W. Tyson, Justin R. Seymour, Roman Stocker

    Microbial interactions influence the productivity and biogeochemistry of the ocean, yet they occur in miniscule volumes that cannot be sampled by traditional oceanographic techniques. To investigate the behaviours of marine microorganisms at spatially relevant scales, we engineered an in situ chemotaxis assay (ISCA) based on microfluidic technology. Here, we describe the fabrication, testing and first field results of the ISCA, demonstrating its value in accessing the microbial behaviours that shape marine ecosystems.

    更新日期:2017-08-28
  • Efficient invasion by Toxoplasma depends on the subversion of host protein networks
    Nat. Microbiol. Pub Date : 2017-08-28
    Amandine Guérin, Rosa Milagros Corrales, Michele L. Parker, Mauld H. Lamarque, Damien Jacot, Hiba El Hajj, Dominique Soldati-Favre, Martin J. Boulanger, Maryse Lebrun

    Apicomplexan parasites are important pathogens of humans and domestic animals, including Plasmodium species (the agents of malaria) and Toxoplasma gondii, which is responsible for toxoplasmosis. They replicate within the cells of their animal hosts, to which they gain access using a unique parasite-driven invasion process. At the core of the invasion machine is a structure at the interface between the invading parasite and host cell called the moving junction (MJ)1. The MJ serves as both a molecular doorway to the host cell and an anchor point enabling the parasite to engage its motility machinery to drive the penetration of the host cell2, ultimately yielding a protective vacuole3. The MJ is established through self-assembly of parasite proteins at the parasite–host interface4. However, it is unknown whether host proteins are subverted for MJ formation. Here, we show that Toxoplasma parasite rhoptry neck proteins (RON2, RON4 and RON5) cooperate to actively recruit the host CIN85, CD2AP and the ESCRT-I components ALIX and TSG101 to the MJ during invasion. We map the interactions in detail and demonstrate that the parasite mimics and subverts conserved binding interfaces with remarkable specificity. Parasite mutants unable to recruit these host proteins show inefficient host cell invasion in culture and attenuated virulence in mice. This study reveals molecular mechanisms by which parasites subvert widely conserved host machinery to force highly efficient host cell access.

    更新日期:2017-08-28
  • Viral pathogenesis: Unlocking Ebola persistence
    Nat. Microbiol. Pub Date : 2017-08-24
    Trina Racine, Gary P. Kobinger

    Viral pathogenesis: Unlocking Ebola persistence Nature Microbiology, Published online: 24 August 2017; doi:10.1038/nmicrobiol.2017.124 The 2013–2016 West African Ebola virus outbreak evidenced that the virus can persist in survivors long-term, leading to sequelae and risks of new transmission chains. Ebola virus has now been shown to behave similarly in rhesus macaques, enabling their use to study persistence and intervention strategies.

    更新日期:2017-08-24
  • Stress and stability: applying the Anna Karenina principle to animal microbiomes
    Nat. Microbiol. Pub Date : 2017-08-24
    Jesse R. Zaneveld, Ryan McMinds, Rebecca Vega Thurber

    All animals studied to date are associated with symbiotic communities of microorganisms. These animal microbiotas often play important roles in normal physiological function and susceptibility to disease; predicting their responses to perturbation represents an essential challenge for microbiology. Most studies of microbiome dynamics test for patterns in which perturbation shifts animal microbiomes from a healthy to a dysbiotic stable state. Here, we consider a complementary alternative: that the microbiological changes induced by many perturbations are stochastic, and therefore lead to transitions from stable to unstable community states. The result is an ‘Anna Karenina principle’ for animal microbiomes, in which dysbiotic individuals vary more in microbial community composition than healthy individuals—paralleling Leo Tolstoy's dictum that “all happy families look alike; each unhappy family is unhappy in its own way”. We argue that Anna Karenina effects are a common and important response of animal microbiomes to stressors that reduce the ability of the host or its microbiome to regulate community composition. Patterns consistent with Anna Karenina effects have been found in systems ranging from the surface of threatened corals exposed to above-average temperatures, to the lungs of patients suffering from HIV/AIDs. However, despite their apparent ubiquity, these patterns are easily missed or discarded by some common workflows, and therefore probably underreported. Now that a substantial body of research has established the existence of these patterns in diverse systems, rigorous testing, intensive time-series datasets and improved stochastic modelling will help to explore their importance for topics ranging from personalized medicine to theories of the evolution of host–microorganism symbioses.

    更新日期:2017-08-24
  • Structural biology: Loading T4SS substrates
    Nat. Microbiol. Pub Date : 2017-08-24
    Peter J. Christie

    Structural biology: Loading T4SS substrates Nature Microbiology, Published online: 24 August 2017; doi:10.1038/nmicrobiol.2017.125 Structural analyses of the type IV coupling protein of the Dot/Icm type IV secretion system from Legionella pneumophila reveal how this platform recruits a plethora of substrates for translocation.

    更新日期:2017-08-24
  • Marine microbiology: Roommates in space and time
    Nat. Microbiol. Pub Date : 2017-08-24
    Meinhard Simon

    Marine microbiology: Roommates in space and time Nature Microbiology, Published online: 24 August 2017; doi:10.1038/nmicrobiol.2017.122 Proteomics analyses reveal how the long-term coexistence of the marine picocyanobacterium Synechococcus and the heterotroph Ruegeria pomeroyi, of the globally abundant marine Roseobacter group, is based on the mutual and beneficial recycling of inorganic and organic nitrogen compounds.

    更新日期:2017-08-24
  • Change advice on antibiotics with caution
    Nat. Microbiol. Pub Date : 2017-08-24

    Change advice on antibiotics with caution Nature Microbiology, Published online: 24 August 2017; doi:10.1038/nmicrobiol.2017.126 The recommendation that antibiotic courses are always completed should be dropped according to a recent analysis. While a welcome addition to discussion on the role of stewardship in tackling resistance, caution should be applied before advice on prescription practices and communication with patients is altered.

    更新日期:2017-08-24
  • Translational fidelity and mistranslation in the cellular response to stress
    Nat. Microbiol. Pub Date : 2017-08-24
    Kyle Mohler, Michael Ibba

    Faithful translation of mRNA into the corresponding polypeptide is a complex multistep process, requiring accurate amino acid selection, transfer RNA (tRNA) charging and mRNA decoding on the ribosome. Key players in this process are aminoacyl-tRNA synthetases (aaRSs), which not only catalyse the attachment of cognate amino acids to their respective tRNAs, but also selectively hydrolyse incorrectly activated non-cognate amino acids and/or misaminoacylated tRNAs. This aaRS proofreading provides quality control checkpoints that exclude non-cognate amino acids during translation, and in so doing helps to prevent the formation of an aberrant proteome. However, despite the intrinsic need for high accuracy during translation, and the widespread evolutionary conservation of aaRS proofreading pathways, requirements for translation quality control vary depending on cellular physiology and changes in growth conditions, and translation errors are not always detrimental. Recent work has demonstrated that mistranslation can also be beneficial to cells, and some organisms have selected for a higher degree of mistranslation than others. The aims of this Review Article are to summarize the known mechanisms of protein translational fidelity and explore the diversity and impact of mistranslation events as a potentially beneficial response to environmental and cellular stress.

    更新日期:2017-08-24
  • Broadly protective murine monoclonal antibodies against influenza B virus target highly conserved neuraminidase epitopes
    Nat. Microbiol. Pub Date : 2017-08-21
    Teddy John Wohlbold, Kira A. Podolsky, Veronika Chromikova, Ericka Kirkpatrick, Veronica Falconieri, Philip Meade, Fatima Amanat, Jessica Tan, Benjamin R. tenOever, Gene S. Tan, Sriram Subramaniam, Peter Palese, Florian Krammer

    A substantial proportion of influenza-related childhood deaths are due to infection with influenza B viruses, which co-circulate in the human population as two antigenically distinct lineages defined by the immunodominant receptor binding protein, haemagglutinin. While broadly cross-reactive, protective monoclonal antibodies against the haemagglutinin of influenza B viruses have been described, none targeting the neuraminidase, the second most abundant viral glycoprotein, have been reported. Here, we analyse a panel of five murine anti-neuraminidase monoclonal antibodies that demonstrate broad binding, neuraminidase inhibition, in vitro antibody-dependent cell-mediated cytotoxicity and in vivo protection against influenza B viruses belonging to both haemagglutinin lineages and spanning over 70 years of antigenic drift. Electron microscopic analysis of two neuraminidase–antibody complexes shows that the conserved neuraminidase epitopes are located on the head of the molecule and that they are distinct from the enzymatic active site. In the mouse model, one therapeutic dose of antibody 1F2 was more protective than the current standard of treatment, oseltamivir, given twice daily for six days.

    更新日期:2017-08-21
  • A plasmid from an Antarctic haloarchaeon uses specialized membrane vesicles to disseminate and infect plasmid-free cells
    Nat. Microbiol. Pub Date : 2017-08-21
    Susanne Erdmann, Bernhard Tschitschko, Ling Zhong, Mark J. Raftery, Ricardo Cavicchioli

    The major difference between viruses and plasmids is the mechanism of transferring their genomic information between host cells. Here, we describe the archaeal plasmid pR1SE from an Antarctic species of haloarchaea that transfers via a mechanism similar to a virus. pR1SE encodes proteins that are found in regularly shaped membrane vesicles, and the vesicles enclose the plasmid DNA. The released vesicles are capable of infecting a plasmid-free strain, which then gains the ability to produce plasmid-containing vesicles. pR1SE can integrate and replicate as part of the host genome, resolve out with fragments of host DNA incorporated or portions of the plasmid left behind, form vesicles and transfer to new hosts. The pR1SE mechanism of transfer of DNA could represent the predecessor of a strategy used by viruses to pass on their genomic DNA and fulfil roles in gene exchange, supporting a strong evolutionary connection between plasmids and viruses.

    更新日期:2017-08-21
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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