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  • Black Truffle, a Hermaphrodite with Forced Unisexual Behaviour
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-13
    Marc-André Selosse, Laure Schneider-Maunoury, Elisa Taschen, François Rousset, Franck Richard

    The life cycle of the black truffle (Tuber melanosporum) includes a mating before sporulation: although the species is hermaphroditic, mating turns out to involve parents with very different features, that mostly behave as male or female only, suggesting that this species undergoes forced dioecism.

  • Ecological Insights into the Dynamics of Plant Biomass-Degrading Microbial Consortia
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-22
    Diego Javier Jiménez, Francisco Dini-Andreote, Kristen M. DeAngelis, Steven W. Singer, Joana Falcão Salles, Jan Dirk van Elsas

    Plant biomass (PB) is an important resource for biofuel production. However, the frequent lack of efficiency of PB saccharification is still an industrial bottleneck. The use of enzyme cocktails produced from PB-degrading microbial consortia (PB-dmc) is a promising approach to optimize this process. Nevertheless, the proper use and manipulation of PB-dmc depends on a sound understanding of the ecological processes and mechanisms that exist in these communities. This Opinion article provides an overview of arguments as to how spatiotemporal nutritional fluxes influence the successional dynamics and ecological interactions (synergism versus competition) between populations in PB-dmc. The themes of niche occupancy, ‘sugar cheaters’, minimal effective consortium, and the Black Queen Hypothesis are raised as key subjects that foster our appraisal of such systems. Here we provide a conceptual framework that describes the critical topics underpinning the ecological basis of PB-dmc, giving a solid foundation upon which further prospective experimentation can be developed.

  • The Hsp90 Chaperone Network Modulates Candida Virulence Traits
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-23
    Teresa R. O’Meara, Nicole Robbins, Leah E. Cowen

    Hsp90 is a conserved molecular chaperone that facilitates the folding and function of client proteins. Hsp90 function is dynamically regulated by interactions with co-chaperones and by post-translational modifications. In the fungal pathogen Candida albicans, Hsp90 enables drug resistance and virulence by stabilizing diverse signal transducers. Here, we review studies that have unveiled regulators of Hsp90 function, as well as downstream effectors that govern the key virulence traits of morphogenesis and drug resistance. We highlight recent work mapping the Hsp90 genetic network in C. albicans under diverse environmental conditions, and how these interactions provide insight into circuitry important for drug resistance, morphogenesis, and virulence. Ultimately, elucidating the Hsp90 chaperone network will aid in the development of therapeutics to treat fungal disease.

  • At the Nexus of Antibiotics and Metals: The Impact of Cu and Zn on Antibiotic Activity and Resistance
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-17
    Keith Poole

    Environmental influences on antibiotic activity and resistance can wreak havoc with in vivo antibiotic efficacy and, ultimately, antimicrobial chemotherapy. In nature, bacteria encounter a variety of metal ions, particularly copper (Cu) and zinc (Zn), as contaminants in soil and water, as feed additives in agriculture, as clinically-used antimicrobials, and as components of human antibacterial responses. Importantly, there is a growing body of evidence for Cu/Zn driving antibiotic resistance development in metal-exposed bacteria, owing to metal selection of genetic elements harbouring both metal and antibiotic resistance genes, and metal recruitment of antibiotic resistance mechanisms. Many classes of antibiotics also form complexes with metal cations, including Cu and Zn, and this can hinder (or enhance) antibiotic activity. This review highlights the ways in which Cu/Zn influence antibiotic resistance development and antibiotic activity, and in so doing impact in vivo antibiotic efficacy.

  • Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-15
    Jasper Adriaan Soppe, Robert Jan Lebbink

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy. Here, we review recent CRISPR/Cas9-based approaches to combat specific human viruses in humans and discuss challenges that need to be overcome before CRISPR/Cas9 may be used in the clinic as an antiviral strategy.

  • Gut Microbiota Dysbiosis in Postweaning Piglets: Understanding the Keys to Health
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-08
    Raphaële Gresse, Frédérique Chaucheyras-Durand, Mickaël Alain Fleury, Tom Van de Wiele, Evelyne Forano, Stéphanie Blanquet-Diot

    Weaning is a critical event in the pig’s life cycle, frequently associated with severe enteric infections and overuse of antibiotics; this raises serious economic and public health concerns. In this review, we explain why gut microbiota dysbiosis, induced by abrupt changes in the diet and environment of piglets, emerges as a leading cause of post-weaning diarrhea, even if the exact underlying mechanisms remain unclear. Then, we focus on nonantimicrobial alternatives, such as zinc oxide, essential oils, and prebiotics or probiotics, which are currently evaluated to restore intestinal balance and allow a better management of the crucial weaning transition. Finally, we discuss how in vitro models of the piglet gut could be advantageously used as a complement to ex vivo and in vivo studies for the development and testing of new feed additives.

  • Opening Pandora’s Box: Mechanisms of Mycobacterium tuberculosis Resuscitation
    Trends Microbiol. (IF 11.02) Pub Date : 2017-09-11
    Ashley V. Veatch, Deepak Kaushal

    Mycobacterium tuberculosis (Mtb) characteristically causes an asymptomatic infection. While this latent tuberculosis infection (LTBI) is not contagious, reactivation to active tuberculosis disease (TB) causes the patient to become infectious. A vaccine has existed for TB for a century, while drug treatments have been available for over 70 years; despite this, TB remains a major global health crisis. Understanding the factors which allow the bacillus to control responses to host stress and mechanisms leading to latency are critical for persistence. Similarly, molecular switches which respond to reactivation are important. Recently, research in the field has sought to focus on reactivation, employing system-wide approaches and animal models. Here, we describe the current work that has been done to elucidate the mechanisms of reactivation and stop reactivation in its tracks.

  • Horizontal Gene Transfer and Ecosystem Function Dynamics
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-24
    Maarten van de Guchte

    Horizontal gene transfer can provide bacteria with new functions that confer an important competitive advantage, and is therefore likely to affect the dynamics of bacterial ecosystems. Two studies by Wolfe et al. and Bonham et al. prepare the way to study this hypothesis in a model ecosystem with reproducible properties.

  • Zika Virus: Mechanisms of Infection During Pregnancy
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-31
    Nicholas J.C. King, Mauro M. Teixeira, Suresh Mahalingam

    Immune status changes during pregnancy, with pro-inflammatory and anti-inflammatory contexts at different stages, making pregnant women potentially more susceptible to various infections. Infection by Zika virus during pregnancy can cause developmental damage to the fetus, and the altered immune response during pregnancy could contribute to disease during Zika infection.

  • Metabolic Integration of Bacterial Endosymbionts through Antimicrobial Peptides
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-23
    Peter Mergaert, Yoshitomo Kikuchi, Shuji Shigenobu, Eva C.M. Nowack

    Antimicrobial peptides (AMPs) are massively produced by eukaryotic hosts during symbiotic interactions with bacteria. Among other roles, these symbiotic AMPs have the capacity to permeabilize symbiont membranes and facilitate metabolite flow across the host–symbiont interface. We propose that an ancestral role of these peptides is to facilitate metabolic exchange between the symbiotic partners through membrane permeabilization. This function may be particularly critical for integration of endosymbiont and host metabolism in interactions involving bacteria with strongly reduced genomes lacking most small metabolite transporters. Moreover, AMPs could have acted in a similar way at the onset of plastid and mitochondrion evolution, after a host cell took up a bacterium and needed to extract nutrients from it in the absence of dedicated solute transporters.

  • Epidemiology, Evolution, and Pathogenesis of H7N9 Influenza Viruses in Five Epidemic Waves since 2013 in China
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-19
    Shuo Su, Min Gu, Di Liu, Jie Cui, George F. Gao, Jiyong Zhou, Xiufan Liu

    H7N9 influenza viruses were first isolated in 2013 and continue to cause human infections. H7N9 infections represent an ongoing public health threat that has resulted in 1344 cases with 511 deaths as of April 9, 2017. This highlights the continued threat posed by the current poultry trade and live poultry market system in China. Until now, there have been five H7N9 influenza epidemic waves in China; however, the steep increase in the number of humans infected with H7N9 viruses observed in the fifth wave, beginning in October 2016, the spread into western provinces, and the emergence of highly pathogenic (HP) H7N9 influenza outbreaks in chickens and infection in humans have caused domestic and international concern. In this review, we summarize and compare the different waves of H7N9 regarding their epidemiology, pathogenesis, evolution, and characteristic features, and speculate on factors behind the recent increase in the number of human cases and sudden outbreaks in chickens. The continuous evolution of the virus poses a long-term threat to public health and the poultry industry, and thus it is imperative to strengthen prevention and control strategies.

  • ‘Omic’ Approaches to Study Uropathogenic Escherichia coli Virulence
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-24
    Alvin W. Lo, Danilo G. Moriel, Minh-Duy Phan, Benjamin L. Schulz, Timothy J. Kidd, Scott A. Beatson, Mark A. Schembri

    Uropathogenic Escherichia coli (UPEC) is a pathogen of major significance to global human health and is strongly associated with rapidly increasing antibiotic resistance. UPEC is the primary cause of urinary tract infection (UTI), a disease that involves a complicated pathogenic pathway of extracellular and intracellular lifestyles during interaction with the host. The application of multiple ‘omic’ technologies, including genomics, transcriptomics, proteomics, and metabolomics, has provided enormous knowledge to our understanding of UPEC biology. Here we outline this progress and present a view for future developments using these exciting forefront technologies to fully comprehend UPEC pathogenesis in the context of infection.

  • Capsid-Dependent Host Factors in HIV-1 Infection
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-18
    Masahiro Yamashita, Alan N. Engelman

    After invasion of a susceptible target cell, HIV-1 completes the early phase of its life cycle upon integration of reverse-transcribed viral DNA into host chromatin. The viral capsid, a conical shell encasing the viral ribonucleoprotein complex, along with its constitutive capsid protein, plays essential roles at virtually every step in the early phase of the viral life cycle. Recent work has begun to reveal how the viral capsid interacts with specific cellular proteins to promote these processes. At the same time, cellular restriction factors target the viral capsid to thwart infection. Comprehensive understanding of capsid–host interactions that promote or impede HIV-1 infection may provide unique insight to exploit for novel therapeutic interventions.

  • Antimycobacterial Metabolism: Illuminating Mycobacterium tuberculosis Biology and Drug Discovery
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-13
    Divya Awasthi, Joel S. Freundlich

    Bacteria are capable of performing a number of biotransformations that may activate or deactivate xenobiotics. Recent efforts have utilized metabolomics techniques to study the fate of small-molecule antibacterials within the targeted organism. Examples involving Mycobacterium tuberculosis are reviewed and analyzed with regard to the insights they provide as to both activation and deactivation of the antibacterial. The studies, in particular, shed light on biosynthetic transformations performed by M. tuberculosis while suggesting avenues for the evolution of chemical tools, highlighting potential areas for drug discovery, and mechanisms of approved drugs. A two-pronged approach investigating the metabolism of antibacterials within both the host and bacterium is outlined and will be of value to both the chemical biology and drug discovery fields.

  • Protein Acetylation and Its Role in Bacterial Virulence
    Trends Microbiol. (IF 11.02) Pub Date : 2017-04-24
    Jie Ren, Yu Sang, Jie Lu, Yu-Feng Yao

    Protein acetylation is a universal post-translational modification which is found in both eukaryotes and prokaryotes. This process is achieved enzymatically by the protein acetyltransferase Pat, and nonenzymatically by metabolic intermediates (e.g., acetyl phosphate) in bacteria. Protein acetylation plays a role in bacterial chemotaxis, metabolism, DNA replication, and other cellular processes. Recently, accumulating evidence has suggested that protein acetylation might be involved in bacterial virulence because a number of bacterial virulence factors are acetylated. In this review, we summarize the progress in understanding bacterial protein acetylation and discuss how it mediates bacterial virulence.

  • Variation, Indispensability, and Masking in the M protein
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-31
    Partho Ghosh

    The M protein is the major surface-associated virulence factor of group A Streptococcus (GAS) and an antigenically variable target of host immunity. How selection pressures to escape immune recognition, maintain indispensable functions, and mask vulnerabilities have shaped the sequences of the >220 M protein types is unclear. Recent experiments have shed light on this question by showing that, hidden within the antigenic variability of many M protein types, are sequence patterns conserved for recruiting human C4b-binding protein (C4BP). Other host factors may be recruited in a similar manner by conserved but hidden sequence patterns in the M protein. The identification of such patterns may be applicable to the development of a GAS vaccine.

  • Bacterial Tubulins: A Eukaryotic-Like Microtubule Cytoskeleton
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-28
    Sylvain Trépout, Anne Marie Wehenkel

    Ever since their discovery, bacterial tubulins, found in several Prosthecobacter species, have raised curiosity as they are closely related to eukaryotic tubulin. Deng and colleagues now present new evidence for the functional homology of the two cytoskeletal systems where in vitro reconstituted Btub-microtubules display eukaryote-like biochemical and dynamic properties.

  • Phagocytes, Antibiotics, and Self-Limiting Bacterial Infections
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-24
    Bruce R. Levin, Fernando Baquero, Peter (Pierre) Ankomah, Ingrid C. McCall

    Most antibiotic use in humans is to reduce the magnitude and term of morbidity of acute, community-acquired infections in immune competent patients, rather than to save lives. Thanks to phagocytic leucocytes and other host defenses, the vast majority of these infections are self-limiting. Nevertheless, there has been a negligible amount of consideration of the contribution of phagocytosis and other host defenses in the research for, and the design of, antibiotic treatment regimens, which hyper-emphasizes antibiotics as if they were the sole mechanism responsible for the clearance of infections. Here, we critically review this approach and its limitations. With the aid of a heuristic mathematical model, we postulate that if the rate of phagocytosis is great enough, for acute, normally self-limiting infections, then (i) antibiotics with different pharmacodynamic properties would be similarly effective, (ii) low doses of antibiotics can be as effective as high doses, and (iii) neither phenotypic nor inherited antibiotic resistance generated during therapy are likely to lead to treatment failure.

  • Women and Their Microbes: The Unexpected Friendship
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-23
    Jessica A. Younes, Elke Lievens, Ruben Hummelen, Rebecca van der Westen, Gregor Reid, Mariya I. Petrova

    Communities of microbiota have been associated with numerous health outcomes, and while much emphasis has been placed on the gastrointestinal niche, there is growing interest in the microbiome specific for female reproductive health and the health of their offspring. The vaginal microbiome plays an essential role not only in health and dysbiosis, but also potentially in successful fertilization and healthy pregnancies. In addition, microbial communities have been isolated from formerly forbidden sterile niches such as the placenta, breast, uterus, and Fallopian tubes, strongly suggesting an additional microbial role in women’s health. A combination of maternally linked prenatal, birth, and postnatal factors, together with environmental and medical interventions, influence early and later life through the microbiome. Here, we review the role of microbes in female health focusing on the vaginal tract and discuss how male and female reproductive microbiomes are intertwined with conception and how mother–child microbial transfer is a key determinant in infant health, and thus the next generation.

  • Visualization of IAV Genomes at the Single-Cell Level
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-23
    Dan Wang, Wenjun Ma

    Different influenza A viruses (IAVs) infect the same cell in a host, and can subsequently produce new viruses through genome reassortment. By combining padlock probe RNA labeling with a single-cell analysis, a new approach effectively captures IAV genome trafficking and defines a time window for genome reassortment from same-cell coinfections.

  • Archaea Are Interactive Components of Complex Microbiomes
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-18
    Christine Moissl-Eichinger, Manuela Pausan, Julian Taffner, Gabriele Berg, Corinna Bang, Ruth A. Schmitz

    Recent findings have shaken our picture of the biology of the archaea and revealed novel traits beyond archaeal extremophily and supposed ‘primitiveness’. The archaea constitute a considerable fraction of the Earth’s ecosystems, and their potential to shape their surroundings by a profound interaction with their biotic and abiotic environment has been recognized. Moreover, archaea have been identified as a substantial component, or even as keystone species, in complex microbiomes – in the environment or accompanying a holobiont. Species of the Euryarchaeota (methanogens, halophiles) and Thaumarchaeota, in particular, have the capacity to coexist in plant, animal, and human microbiomes, where syntrophy allows them to thrive under energy-deficiency stress. Due to methodological limitations, the archaeome remains mysterious, and many questions with respect to potential pathogenicity, function, and structural interactions with their host and other microorganisms remain.

  • The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-17
    Karin Hoppe-Seyler, Felicitas Bossler, Julia A. Braun, Anja L. Herrmann, Felix Hoppe-Seyler

    Human papillomavirus (HPV)-induced cancers are expected to remain a major health problem worldwide for decades. The growth of HPV-positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes which act in concert with still poorly defined cellular alterations. E6/E7 constitute attractive therapeutic targets since E6/E7 inhibition rapidly induces senescence in HPV-positive cancer cells. This cellular response is linked to the reconstitution of the antiproliferative p53 and pRb pathways, and to prosenescent mTOR signaling. Hypoxic HPV-positive cancer cells could be a major obstacle for treatment strategies targeting E6/E7 since they downregulate E6/E7 but evade senescence through hypoxia-induced mTOR impairment. Prospective E6/E7 inhibitors may therefore benefit from a combination with treatment strategies directed against hypoxic tumor cells.

  • Mechanisms of Hepatitis B Virus Persistence
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-16
    Kuen-Nan Tsai, Cheng-Fu Kuo, Jing-Hsiung James Ou

    Hepatitis B virus (HBV) chronically infects 250 million people worldwide, resulting in nearly one million deaths annually. Studies in recent years have significantly improved our knowledge on the mechanisms of HBV persistence. HBV uses multiple pathways to harness host innate immunity to enhance its replication. It can also take advantage of the developing immune system and the not-yet-stabilized gut microbiota of young children to facilitate its persistence, and use maternal viral e antigen to educate immunity of the offspring to support its persistence after vertical transmission. The knowledge gained from these recent studies paves the way for the development of new therapies for the treatment of chronic HBV infection, which has so far been very challenging.

  • Genomics and Ecology of Novel N2O-Reducing Microorganisms
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-10
    Sara Hallin, Laurent Philippot, Frank E. Löffler, Robert A. Sanford, Christopher M. Jones

    Microorganisms with the capacity to reduce the greenhouse gas nitrous oxide (N2O) to harmless dinitrogen gas are receiving increased attention due to increasing N2O emissions (and our need to mitigate climate change) and to recent discoveries of novel N2O-reducing bacteria and archaea. The diversity of denitrifying and nondenitrifying microorganisms with capacity for N2O reduction was recently shown to be greater than previously expected. A formerly overlooked group (clade II) in the environment include a large fraction of nondenitrifying N2O reducers, which could be N2O sinks without major contribution to N2O formation. We review the recent advances about fundamental understanding of the genomics, physiology, and ecology of N2O reducers and the importance of these findings for curbing N2O emissions.

  • Zika Virus Protease: An Antiviral Drug Target
    Trends Microbiol. (IF 11.02) Pub Date : 2017-08-05
    CongBao Kang, Thomas H. Keller, Dahai Luo

    The recent outbreak of Zika virus (ZIKV) infection has caused global concern due to its link to severe damage to the brain development of foetuses and neuronal complications in adult patients. A worldwide research effort has been undertaken to identify effective and safe treatment and vaccination options. Among the proposed viral and host components, the viral NS2B-NS3 protease represents an attractive drug target due to its essential role in the virus life cycle. Here, we outline recent progress in studies on the Zika protease. Biochemical, biophysical, and structural studies on different protease constructs provide new insight into the structure and activity of the protease. The unlinked construct displays higher enzymatic activity and better mimics the native state of the enzyme and therefore is better suited for drug discovery. Furthermore, the structure of the free enzyme adopts a closed conformation and a preformed active site. The availability of a lead fragment hit and peptide inhibitors, as well as the attainability of soakable crystals, suggest that the unlinked construct is a promising tool for drug discovery.

  • A Single Substitution Changes Zika Virus Infectivity in Mosquitoes
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-10
    Guan-Zhu Han

    Zika virus (ZIKV) has caused outbreaks in the Pacific and the Americas. The mechanism underlying the recent ZIKV epidemic remains obscure. A recent study reveals that an amino acid substitution is associated with increased infectivity of ZIKV in the Aedes aegypti mosquito.

  • What Does Not Kill You Makes You Stronger
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-26
    Miles T. Wetherington, Juan E. Keymer

    Colicin production is an extreme form of labor division; cells lyse after making the toxin! Stochastic phenotype switching allows producers to outcompete sensitive strains since colicin release frees up vacancy. If patch dynamics does not kill you, it stimulates adaptation to a dynamic habitat landscape which selects for rapid dispersal.

  • Micronutrient Deficiencies and the Human Gut Microbiota
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-20
    Núria Mach, Allison Clark

    Little is known about how micronutrient deficiencies affect the human gut microbiota. A study by Hibberd et al. illustrates how these deficiencies affect the composition and function of gut microbiota, and further, how different species realize changes in gene expression and cellular metabolism to cope with micronutrient shortages.

  • Microbiome-on-a-Chip: New Frontiers in Plant–Microbiota Research
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-24
    Claire E. Stanley, Marcel G.A. van der Heijden

    An enigmatic concoction of interactions between microbes and hosts takes place below ground, yet the function(s) of the individual components in this complex playground are far from understood. This Forum article highlights how microfluidic – or ‘Microbiome-on-a-Chip’ – technology could help to shed light on such relationships, opening new frontiers in plant–microbiota research.

  • Bacteria–Bacteriophage Coevolution in the Human Gut: Implications for Microbial Diversity and Functionality
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-22
    Pauline D. Scanlan

    Antagonistic coevolution (AC) between bacteria and bacteriophages plays a key role in driving and maintaining microbial diversity. Consequently, AC is predicted to affect all levels of biological organisation, from the individual to ecosystem scales. Nonetheless, we know nothing about bacteria–bacteriophage AC in perhaps the most important and clinically relevant microbial ecosystem known to humankind – the human gut microbiome. In this opinion piece I review current research on bacteria–phage AC in in vitro and natural populations of microbes. I then examine the evidence and discuss the potential role of AC in driving observed patterns of intra- and interindividual variation in the gut microbiome together with detailing the potential functional consequences of such AC-driven microbial variation for human health and disease.

  • Genome Surfing As Driver of Microbial Genomic Diversity
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-07
    Mallory J. Choudoir, Kevin Panke-Buisse, Cheryl P. Andam, Daniel H. Buckley

    Historical changes in population size, such as those caused by demographic range expansions, can produce nonadaptive changes in genomic diversity through mechanisms such as gene surfing. We propose that demographic range expansion of a microbial population capable of horizontal gene exchange can result in genome surfing, a mechanism that can cause widespread increase in the pan-genome frequency of genes acquired by horizontal gene exchange. We explain that patterns of genetic diversity within Streptomyces are consistent with genome surfing, and we describe several predictions for testing this hypothesis both in Streptomyces and in other microorganisms.

  • Cell Death Pathway That Monitors Spore Morphogenesis
    Trends Microbiol. (IF 11.02) Pub Date : 2017-04-10
    Amanda R. Decker, Kumaran S. Ramamurthi

    The use of quality control mechanisms to stall developmental pathways or completely remove defective cells from a population is a widespread strategy to ensure the integrity of morphogenetic programs. Endospore formation (sporulation) is a well conserved microbial developmental strategy in the Firmicutes phylum wherein a progenitor cell that faces starvation differentiates to form a dormant spore. Despite the conservation of this strategy, it has been unclear what selective pressure maintains the fitness of this developmental program, composed of hundreds of unique genes, during multiple rounds of vegetative growth when sporulation is not required. Recently, a quality control pathway was discovered in Bacillus subtilis which monitors the assembly of the spore envelope and specifically eliminates, through cell lysis, sporulating cells that assemble the envelope incorrectly. Here, we review the use of checkpoints that govern the entry into sporulation in B. subtilis and discuss how the use of regulated cell death pathways during bacterial development may help maintain the fidelity of the sporulation program in the species.

  • KSHV microRNAs: Tricks of the Devil
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-02
    Jie Qin, Wan Li, Shou-Jiang Gao, Chun Lu

    Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi’s sarcoma (KS), a vascular tumor frequently found in immunodeficient individuals. KSHV encodes 12 pre-microRNAs (pre-miRNAs), which are processed into 25 mature microRNAs (miRNAs). KSHV miRNAs maintain KSHV latency, enhance angiogenesis and dissemination of the infected cells, and interfere with the host immune system by regulating viral and cellular gene expression, ultimately contributing to KS development. In this review, we briefly introduce the biogenesis of miRNAs and then describe the recent advances in defining the roles and mechanisms of action of KSHV miRNAs in KS development.

  • Sweet New Roles for Protein Glycosylation in Prokaryotes
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-21
    Jerry Eichler, Michael Koomey

    Long-held to be a post-translational modification unique to Eukarya, it is now clear that both Bacteria and Archaea also perform protein glycosylation, namely the covalent attachment of mono- to polysaccharides to specific protein targets. At the same time, many of the roles assigned to this protein-processing event in eukaryotes, such as guiding protein folding/quality control, intracellular trafficking, dictating cellular recognition events and others, do not apply or are even irrelevant to prokaryotes. As such, protein glycosylation must serve novel functions in Bacteria and Archaea. Recent efforts have begun to elucidate some of these prokaryote-specific roles, which are addressed in this review.

  • Shapeshifting to Survive: Shape Determination and Regulation in Caulobacter crescentus
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-27
    Selamawit Abi Woldemeskel, Erin D. Goley

    Bacterial cell shape is a genetically encoded and inherited feature that is optimized for efficient growth, survival, and propagation of bacteria. In addition, bacterial cell morphology is adaptable to changes in environmental conditions. Work in recent years has demonstrated that individual features of cell shape, such as length or curvature, arise through the spatial regulation of cell wall synthesis by cytoskeletal proteins. However, the mechanisms by which these different morphogenetic factors are coordinated and how they may be globally regulated in response to cell cycle and environmental cues are only beginning to emerge. Here, we have summarized recent advances that have been made to understand morphology in the dimorphic Gram-negative bacterium Caulobacter crescentus.

  • Integrating Lung Physiology, Immunology, and Tuberculosis
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-30
    Jordi B. Torrelles, Larry S. Schlesinger

    Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly ‘attacked’ by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several ‘interaction points’ (IPs) which it must overcome to cause infection. These interactions are critical, not only from a pathogenesis perspective but also in considering the effectiveness of therapies and vaccines in the lungs. Here we discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence.

  • Do Shoot the Messenger: PASTA Kinases as Virulence Determinants and Antibiotic Targets
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-19
    Daniel A. Pensinger, Adam J. Schaenzer, John-Demian Sauer

    All domains of life utilize protein phosphorylation as a mechanism of signal transduction. In bacteria, protein phosphorylation was classically thought to be mediated exclusively by histidine kinases as part of two-component signaling systems. However, it is now well appreciated that eukaryotic-like serine/threonine kinases (eSTKs) control essential processes in bacteria. A subset of eSTKs are single-pass transmembrane proteins that have extracellular penicillin-binding-protein and serine/threonine kinase-associated (PASTA) domains which bind muropeptides. In a variety of important pathogens, PASTA kinases have been implicated in regulating biofilms, antibiotic resistance, and ultimately virulence. Although there are limited examples of direct regulation of virulence factors, PASTA kinases are critical for virulence due to their roles in regulating bacterial physiology in the context of stress. This review focuses on the role of PASTA kinases in virulence for a variety of important Gram-positive pathogens and concludes with a discussion of current efforts to develop kinase inhibitors as novel antimicrobials.

  • Navigating the Gut Buffet: Control of Polysaccharide Utilization in Bacteroides spp.
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-18
    Nathan D. Schwalm, Eduardo A. Groisman

    Bacteroides spp. are members of the human gut microbiota that confer myriad benefits on their hosts. Among them is the provision of energy from otherwise indigestible polysaccharides comprising part of the host diet, lining the intestinal mucosal layer, and decorating the surface of other microbes. Bacteroides spp. devote ∼20% of their genomes to the transport and breakdown of a wide variety of polysaccharides, and to the regulation of these processes. Bacteroides spp. rely on different families of transcriptional regulators to ensure that carbohydrate utilization genes are expressed under specific conditions. The regulators and mechanisms controlling carbohydrate utilization are often unique to these gut-dwelling bacteria, and do not conform to those of model organisms.

  • Impact of the Microbiota on Bacterial Infections during Cancer Treatment
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-17
    Jessica Galloway-Peña, Chelcy Brumlow, Samuel Shelburne

    Patients being treated for cancer are at high risk for infectious complications, generally due to colonizing organisms that gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug-resistant organisms, to colonize and subsequently infect humans is largely dependent on protective bacterial species present in the microbiome. Thus, herein we review recent studies demonstrating strong correlations between the microbiome of the oncology patient and infections occurring during chemotherapy. An increased knowledge of the interplay between potential pathogens, protective commensals, and the host immune system may facilitate the development of novel biomarkers or therapeutics that could help ameliorate the toll that infections take during the treatment of cancer.

  • The Other Microeukaryotes of the Coral Reef Microbiome
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-15
    T.D. Ainsworth, A.J. Fordyce, E.F. Camp

    In marine ecosystems microbial communities are critical to ocean function, global primary productivity, and biogeochemical cycles. Both prokaryotic and eukaryotic microbes are essential symbionts and mutualists, nonpathogenic invaders, primary pathogens, have been linked to disease emergence, and can underpin broader ecosystem changes. However, in the effort to determine coral–microbial interactions, the structure and function of the eukaryotic microbes of the microbiome have been studied less. Eukaryotic microbes are important members of the microbiome, constitute entire kingdoms of life, and make important contributions to ecosystem function. Here, we outline the roles of eukaryotic microbes in marine systems and their contribution to ecosystem change, and discuss the microeukaryotic microbiome of corals and coral reefs.

  • Natural-Product Antibiotics: Cues for Modulating Bacterial Biofilm Formation
    Trends Microbiol. (IF 11.02) Pub Date : 2017-07-05
    Loni Townsley, Elizabeth A. Shank

    Cell–cell communication enables bacteria to coordinate their behavior through the production, recognition, and response to chemical signals produced by their microbial neighbors. An important example of coordinated behavior in bacteria is biofilm formation, where individual cells organize into highly complex, matrix-encased communities that differentiate into distinct cell types and divide labor among individual cells. Bacteria rely on environmental cues to influence biofilm development, including chemical cues produced by other microbes. A multitude of recent studies have demonstrated that natural-product antibiotics at subinhibitory concentrations can impact biofilm formation in neighboring microbes, supporting the hypothesis that these compounds may have evolved as signaling molecules that mediate cell–cell interactions. In this review we discuss the role of antibiotics in modulating biofilm formation and interspecies communication in bacteria.

  • Emergence of a Urogenital Pathotype of Neisseria meningitidis
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-22
    Charlene M. Kahler

    Neisseria meningitidis is the causative agent of transmissible sepsis and meningitis in humans. A urogenital pathotype of N. meningitidis as the causative agent of transmissible urethritis in the USA has been recently characterised. This pathotype belongs to clonal complex 11 and has lost capsule production but gained anaerobic growth.

  • Live-Cell Nanoscopy in Antiadhesion Therapy
    Trends Microbiol. (IF 11.02) Pub Date : 2017-05-08
    Joan A. Geoghegan, Timothy J. Foster, Pietro Speziale, Yves F. Dufrêne

    Live-cell nanoscopy has contributed significantly to assessing the inhibition of adhesion of uropathogenic Escherichia coli and Staphylococcus aureus by glycoconjugates and monoclonal antibodies, respectively, and of S. aureus surface attachment and cell–cell association by a synthetic peptide. This new technology shows promise for the development of antiadhesion therapies against bacterial pathogens.

  • Spatial and Temporal Control of Evolution through Replication–Transcription Conflicts
    Trends Microbiol. (IF 11.02) Pub Date : 2017-02-16
    Houra Merrikh

    Evolution could potentially be accelerated if an organism could selectively increase the mutation rate of specific genes that are actively under positive selection. Recently, a mechanism that cells can use to target rapid evolution to specific genes was discovered. This mechanism is driven by gene orientation-dependent encounters between DNA replication and transcription machineries. These encounters increase mutagenesis in lagging-strand genes, where replication–transcription conflicts are severe. Due to the orientation and transcription-dependent nature of this process, conflict-driven mutagenesis can be used by cells to spatially (gene-specifically) and temporally (only upon transcription induction) regulate the rate of gene evolution. Here, I summarize recent findings on this topic, and discuss the implications of increasing mutagenesis rates and accelerating evolution through active mechanisms.

  • Streptomyces Exploration: Competition, Volatile Communication and New Bacterial Behaviours
    Trends Microbiol. (IF 11.02) Pub Date : 2017-02-27
    Stephanie E. Jones, Marie A. Elliot

    Streptomyces bacteria are prolific producers of specialized metabolites, and have a well studied, complex life cycle. Recent work has revealed a new type of Streptomyces growth termed ‘exploration’ – so named for the ability of explorer cells to rapidly traverse solid surfaces. Streptomyces exploration is stimulated by fungal interactions, and is associated with the production of an alkaline volatile organic compound (VOC) capable of inducing exploration by other streptomycetes. Here, we examine Streptomyces exploration from the perspectives of interkingdom interactions, pH-induced morphological switches, and VOC-mediated communication. The phenotypic diversity that can be revealed through microbial interactions and VOC exposure is providing us with insight into novel modes of microbial development, and an opportunity to exploit VOCs to stimulate desired microbial behaviours.

  • The Secrets of Acinetobacter Secretion
    Trends Microbiol. (IF 11.02) Pub Date : 2017-02-16
    Brent S. Weber, Rachel L. Kinsella, Christian M. Harding, Mario F. Feldman

    Infections caused by the bacterial pathogen Acinetobacter baumannii are a mounting concern for healthcare practitioners as widespread antibiotic resistance continues to limit therapeutic treatment options. The biological processes used by A. baumannii to cause disease are not well defined, but recent research has indicated that secreted proteins may play a major role. A variety of mechanisms have now been shown to contribute to protein secretion by A. baumannii and other pathogenic species of Acinetobacter, including a type II secretion system (T2SS), a type VI secretion system (T6SS), autotransporter, and outer membrane vesicles (OMVs). In this review, we summarize the current knowledge of secretion systems in Acinetobacter species, and highlight their unique aspects that contribute to the pathogenicity and persistence of these emerging pathogens.

  • Regulation Mechanisms of Viral IRES-Driven Translation
    Trends Microbiol. (IF 11.02) Pub Date : 2017-02-24
    Kuo-Ming Lee, Chi-Jene Chen, Shin-Ru Shih

    Internal ribosome entry sites (IRESs) can be found in the mRNA of many viruses as well as in cellular genes involved in the stress response, cell cycle, and apoptosis. IRES-mediated translation can occur when dominant cap-dependent translation is inhibited, and viruses can take advantage of this to subvert host translation machinery. In this review, we focus on the four major types of IRES identified in RNA viruses, and outline their distinct structural properties and requirements of translational factors. We further discuss auxiliary host factors known as IRES trans-acting factors (ITAFs), which are involved in the modulation of optimal IRES activity. Currently known strategies employed by viruses to harness ITAFs and regulate IRES activity are also highlighted.

  • Evolutionary Constraints Shaping Streptococcus pyogenes–Host Interactions
    Trends Microbiol. (IF 11.02) Pub Date : 2017-02-16
    Reid V. Wilkening, Michael J. Federle

    Research on the Gram-positive human-restricted pathogen Streptococcus pyogenes (Group A Streptococcus, GAS) has long focused on invasive illness, the most severe manifestations of GAS infection. Recent advances in descriptions of molecular mechanisms of GAS virulence, coupled with massive sequencing efforts to isolate genomes, have allowed the field to better understand the molecular and evolutionary changes leading to pandemic strains. These findings suggest that it is necessary to rethink the dogma involving GAS pathogenesis, and that the most productive avenues for research going forward may be investigations into GAS in its ‘normal’ habitat, the nasopharynx, and its ability to either live with its host in an asymptomatic lifestyle or as an agent of superficial infections. This review will consider these advances, focusing on the natural history of GAS, the evolution of pandemic strains, and novel roles for several key virulence factors that may allow the field to better understand their physiological role.

  • Transcriptional Regulation of Antiviral Interferon-Stimulated Genes
    Trends Microbiol. (IF 11.02) Pub Date : 2017-01-27
    Wenshi Wang, Lei Xu, Junhong Su, Maikel P. Peppelenbosch, Qiuwei Pan

    Interferon-stimulated genes (ISGs) are a group of gene products that coordinately combat pathogen invasions, in particular viral infections. Transcription of ISGs occurs rapidly upon pathogen invasion, and this is classically provoked via activation of the Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway, mainly by interferons (IFNs). However, a plethora of recent studies have reported a variety of non-canonical mechanisms regulating ISG transcription. These new studies are extremely important for understanding the quantitative and temporal differences in ISG transcription under specific circumstances. Because these canonical and non-canonical regulatory mechanisms are essential for defining the nature of host defense and associated detrimental proinflammatory effects, we comprehensively review the state of this rapidly evolving field and the clinical implications of recently acquired knowledge in this respect.

  • Critical Streptococcus suis Virulence Factors: Are They All Really Critical?
    Trends Microbiol. (IF 11.02) Pub Date : 2017-03-06
    Mariela Segura, Nahuel Fittipaldi, Cynthia Calzas, Marcelo Gottschalk

    Streptococcus suis is an important swine pathogen that can be transmitted to humans by contact with diseased animals or contaminated raw pork products. This pathogen possesses a coat of capsular polysaccharide (CPS) that confers protection against the immune system. Yet, the CPS is not the only virulence factor enabling this bacterium to successfully colonize, invade, and disseminate in its host leading to severe systemic diseases such as meningitis and toxic shock-like syndrome. Indeed, recent research developments, cautiously inventoried in this review, have revealed over 100 ‘putative virulence factors or traits’ (surface-associated or secreted components, regulatory genes or metabolic pathways), of which at least 37 have been claimed as being ‘critical’ for virulence. In this review we discuss the current contradictions and controversies raised by this explosion of virulence factors and the future directions that may be conceived to advance and enlighten research on S. suis pathogenesis.

  • Unravelling HIV-1 Latency, One Cell at a Time
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-28
    Yik Lim Kok, Angela Ciuffi, Karin J. Metzner

    A single virus is capable of infecting and replicating in a single cell. Recent advances across single-cell omics technologies – genomics, epigenomics, transcriptomics, epitranscriptomics, proteomics, and metabolomics – will offer unprecedented opportunities to gain more insights into the various aspects of the life cycle of viruses and their impact on the host cell. Here, using the human immunodeficiency virus type 1 (HIV-1) as an example, we summarize the current knowledge and the future potential of single-cell omics in the investigation of an important aspect of the life cycle of HIV-1 that represents a major hurdle in achieving viral eradication, HIV-1 latency.

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.