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  • Glycan Utilization and Cross-Feeding Activities by Bifidobacteria
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-28
    Francesca Turroni, Christian Milani, Sabrina Duranti, Jennifer Mahony, Douwe van Sinderen, Marco Ventura

    Bifidobacteria represent one of the first colonizers of the mammalian gut, where such colonization is facilitated by their saccharolytic capabilities. Genomic analyses of bifidobacteria have revealed intriguing genetic strategies employed by these bacteria to access a variety of dietary and host-produced glycans. Bifidobacterial genome evolution therefore represents a fascinating example of how their chromosomes were molded to contain a large number of genes involved in carbohydrate metabolism. One of the reasons as to why bifidobacteria are such dominant and prevalent members of the (early) microbiota is that they may access glycans in the gut through mutualistic cross-feeding or resource-sharing activities, which is indicative of ‘social behavior’ among bifidobacterial strains.

  • Community Assembly Processes of the Microbial Rare Biosphere
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-14
    Xiu Jia, Francisco Dini-Andreote, Joana Falcão Salles

    Our planet teems with microorganisms that often present a skewed abundance distribution in a local community, with relatively few dominant species coexisting alongside a high number of rare species. Recent studies have demonstrated that these rare taxa serve as limitless reservoirs of genetic diversity, and perform disproportionate types of functions despite their low abundances. However, relatively little is known about the mechanisms controlling rarity and the processes promoting the development of the rare biosphere. Here, we propose the use of multivariate cut-offs to estimate rare species and phylogenetic null models applied to predefined rare taxa to disentangle the relative influences of ecoevolutionary processes mediating the assembly of the rare biosphere. Importantly, the identification of the factors controlling rare species assemblages is critical for understanding the types of rarity, how the rare biosphere is established, and how rare microorganisms fluctuate over spatiotemporal scales, thus enabling prospective predictions of ecosystem responses.

  • Extracellular Vesicle RNA: A Universal Mediator of Microbial Communication?
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-13
    James A. Tsatsaronis, Sandra Franch-Arroyo, Ulrike Resch, Emmanuelle Charpentier

    Both extracellular RNAs and extracellular vesicles (EVs) have recently garnered attention as novel mediators of intercellular communication in eukaryotes and prokaryotes alike. EVs not only permit export of RNA, but also facilitate delivery and trans-kingdom exchange of these and other biomolecules, for instance between microbes and their hosts. In this Opinion article, we propose that EV-mediated export of RNA represents a universal mechanism for interkingdom and intrakingdom communication that is conserved among bacterial, archaeal, and eukaryotic microbes. We speculate how microbes might use EV RNA to influence target cell gene expression or manipulate host immune responses.

  • Achieving a Predictive Understanding of Antimicrobial Stress Physiology through Systems Biology
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-10
    Sean G. Mack, Randi L. Turner, Daniel J. Dwyer

    The dramatic spread and diversity of antibiotic-resistant pathogens has significantly reduced the efficacy of essentially all antibiotic classes, bringing us ever closer to a postantibiotic era. Exacerbating this issue, our understanding of the multiscale physiological impact of antimicrobial challenge on bacterial pathogens remains incomplete. Concerns over resistance and the need for new antibiotics have motivated the collection of omics measurements to provide systems-level insights into antimicrobial stress responses for nearly 20 years. Although technological advances have markedly improved the types and resolution of such measurements, continued development of mathematical frameworks aimed at providing a predictive understanding of complex antimicrobial-associated phenotypes is critical to maximize the utility of multiscale data. Here we highlight recent efforts utilizing systems biology to enhance our knowledge of antimicrobial stress physiology. We provide a brief historical perspective of antibiotic-focused omics measurements, highlight new measurement discoveries and trends, discuss examples and opportunities for integrating measurements with mathematical models, and describe future challenges for the field.

  • Within-Host Evolution of Human Influenza Virus
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-10
    Katherine S. Xue, Louise H. Moncla, Trevor Bedford, Jesse D. Bloom

    The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus’s global evolution.

  • Learning from Noise: How Observing Stochasticity May Aid Microbiology
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-09
    Ariel Amir, Nathalie Q. Balaban

    For many decades, the wedding of quantitative data with mathematical modeling has been fruitful, leading to important biological insights. Here, we review some of the ongoing efforts to gain insights into problems in microbiology – and, in particular, cell-cycle progression and its regulation – through observation and quantitative analysis of the natural fluctuations in the system. We first illustrate this idea by reviewing a classic example in microbiology – the Luria–Delbrück experiment – and discussing how, in that case, useful information was obtained by looking beyond the mean outcome of the experiment, but instead paying attention to the variability between replicates of the experiment. We then switch gears to the contemporary problem of cell cycle progression and discuss in more detail how insights into cell size regulation and, when relevant, coupling between the cell cycle and the circadian clock, can be gained by studying the natural fluctuations in the system and their statistical properties. We end with a more general discussion of how (in this context) the correct level of phenomenological model should be chosen, as well as some of the pitfalls associated with this type of analysis. Throughout this review the emphasis is not on providing details of the experimental setups or technical details of the models used, but rather, in fleshing out the conceptual structure of this particular approach to the problem. For this reason, we choose to illustrate the framework on a rather broad range of problems, and on organisms from all domains of life, to emphasize the commonality of the ideas and analysis used (as well as their differences).

  • Towards Understanding MCR-like Colistin Resistance
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-07
    Jian Sun, Huimin Zhang, Ya-Hong Liu, Youjun Feng

    Antibiotic resistance has become a global public health priority. Polymyxins, a family of cationic polypeptide antibiotics, act as a final line of refuge against severe infections by Gram-negative pathogens with pan-drug resistance. Unfortunately, this last-resort antibiotic has been challenged by the emergence and global spread of mobilized colistin resistance determinants (mcr). Given the fact that it has triggered extensive concerns worldwide, we present here an updated view of MCR-like colistin resistance. These studies provide a basic framework for understanding the molecular epidemiology and resistance mechanism of MCR-like genes. However, further large-scale epidemiology and functional studies are urgently needed to better understand the biology of this clinically important antibiotic resistance.

  • Nitrospira
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-28
    Holger Daims, Michael Wagner

    Download high-res image (362KB) Download full-size image In this infographic, the key metabolic functions of Nitrospira and the role that these bacteria play in nitrification and other processes in the environment is shown. Nitrospira plays pivotal roles in nitrification as an aerobic chemolithoautotrophic nitrite-oxidizing bacterium. These bacteria often occur in close association with ammonia-oxidizing bacteria or archaea that convert ammonia to nitrite, which is further oxidized to nitrate by Nitrospira. However, in ‘reciprocal feeding’ interactions, Nitrospira can also provide ammonia oxidizers with ammonia released from urea or cyanate, which is further nitrified as described above. Recently discovered Nitrospira members even catalyze both nitrification steps alone and are therefore called complete ammonia oxidizers or ‘comammox’ organisms. Some strains of Nitrospira utilize alternative substrates, such as H2 and formate, using oxygen or nitrate as terminal electron acceptor, and can exploit these energy sources concurrently with aerobic nitrite oxidation. This metabolic versatility enables Nitrospira to colonize a broad range of habitats and to sustain shifts in environmental conditions such as changing oxygen concentrations.

  • Hepatitis B Virus
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-27
    Chiaho Shih, Ching-Chun Yang, Gansukh Choijilsuren, Chih-Hsu Chang, An-Ting Liou

    Download high-res image (474KB) Download full-size image This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated. Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription. Its covalently closed circular (ccc) DNA in the nucleus encodes a pregenomic RNA (pgRNA), which can be encapsidated by HBV polymerase. Reverse transcription occurs in the capsids by using the pgRNA as a template for the synthesis of single-stranded linear and then partially double-stranded relaxed circular (rc) DNA. Capsids containing a mature rc DNA genome target to the nucleus for ccc DNA synthesis. Persistent HBV infection is caused mainly by ccc DNA and immune tolerance to HBV antigens in the liver. Unlike acute infection, chronic carriers contain only a low level of HBV core-antigen-specific T cell activity, contributing to the lack of viral clearance.

  • Towards a Natural History of Soil Bacterial Communities
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-06
    Jennifer B.H. Martiny, Kendra E. Walters

    Despite the enormous diversity of bacteria, a recent study reveals that soils are globally dominated by a small list of taxa. Characterizing the traits of these bacteria offers the potential for predicting functional differences among soil communities.

  • Of Mice and Men....and Plants: Comparative Genomics of the Dual Lifestyles of Enteric Pathogens
    Trends Microbiol. (IF 11.02) Pub Date : 2018-03-01
    Max Teplitski, Marcos de Moraes

    Outbreaks of gastrointestinal illness, linked to the consumption of fruits, vegetables, and sprouts, continue to capture the attention of the general public and scientists. The recurrence of these outbreaks, despite heightened producer and consumer awareness, combined with improved sanitation protocols and technology, can be explained by the hypothesis that enteric pathogens, such as nontyphoidal Salmonella spp. and enterovirulent Escherichia coli, have evolved to exploit plants as alternative hosts. This review explores the genetic and genomic context for this hypothesis. Even though gastroenteritis outbreaks associated with the consumption of produce have been caused by a limited number of strains or serovars, robust evidence in support of the polymorphism hypothesis is lacking. While some housekeeping genes with additional virulence functions in animal models contribute to the fitness of enterics within plants, canonical virulence determinants required for animal infections, such as the type III secretion system (T3SS) and effectors, by and large, are of little consequence in interactions with plants. Conversely, despite possessing some functions more commonly found in phytobacteria, human enteric pathogens do not appear to rely on the same strategies for plant colonization. Instead, it is likely that nontyphoidal Salmonella and enterovirulent E. coli have evolved a set of functions distinct from its virulence regulon and from those used by phytopathogens.

  • A Delicate Connection: c-di-AMP Affects Cell Integrity by Controlling Osmolyte Transport
    Trends Microbiol. (IF 11.02) Pub Date : 2017-09-28
    Fabian M. Commichau, Johannes Gibhardt, Sven Halbedel, Jan Gundlach, Jörg Stülke

    Bacteria use second-messenger molecules to adapt to their environment. Several second messengers, among them cyclic di-AMP (c-di-AMP), have been discovered and intensively studied. Interestingly, c-di-AMP is essential for growth of Gram-positive bacteria such as Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus. Many studies demonstrated that perturbation of c-di-AMP metabolism affects the integrity of the bacterial cell envelope. Therefore, it has been assumed that the nucleotide is essential for proper cell envelope synthesis. In this Opinion paper, we propose that the cell envelope phenotypes caused by perturbations of c-di-AMP metabolism can be interpreted differently: c-di-AMP might indirectly control cell envelope integrity by modulating the turgor, a physical variable that needs to be tightly adjusted. We also discuss open questions related to c-di-AMP metabolism that need to be urgently addressed by future studies.

  • The Molecular Basis of Noncanonical Bacterial Morphology
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-19
    Paul D. Caccamo, Yves V. Brun

    Bacteria come in a wide variety of shapes and sizes. The true picture of bacterial morphological diversity is likely skewed due to an experimental focus on pathogens and industrially relevant organisms. Indeed, most of the work elucidating the genes and molecular processes involved in maintaining bacterial morphology has been limited to rod- or coccal-shaped model systems. The mechanisms of shape evolution, the molecular processes underlying diverse shapes and growth modes, and how individual cells can dynamically modulate their shape are just beginning to be revealed. Here we discuss recent work aimed at advancing our knowledge of shape diversity and uncovering the molecular basis for shape generation in noncanonical and morphologically complex bacteria.

  • Clinical Potential of Prefusion RSV F-specific Antibodies
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-17
    Iebe Rossey, Jason S. McLellan, Xavier Saelens, Bert Schepens

    Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in the very young. The RSV fusion protein (F) is essential for virus entry because it mediates viral and host membrane fusion. During this fusion process F is converted from a metastable prefusion conformation into an energetically favored postfusion state. Antibodies that target F can prevent viral entry and reduce disease caused by RSV. During recent years, many prefusion F-specific antibodies have been described. These antibodies typically have stronger RSV-neutralizing activity compared to those that also bind F in the postfusion conformation. Here, we describe how F-specific antibodies protect against RSV and why specifically targeting prefusion F could have great clinical potential.

  • Antibiotic-Resistance Genes in Waste Water
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-13
    Antti Karkman, Thi Thuy Do, Fiona Walsh, Marko P.J. Virta

    Waste water and waste water treatment plants can act as reservoirs and environmental suppliers of antibiotic resistance. They have also been proposed to be hotspots for horizontal gene transfer, enabling the spread of antibiotic resistance genes between different bacterial species. Waste water contains antibiotics, disinfectants, and metals which can form a selection pressure for antibiotic resistance, even in low concentrations. Our knowledge of antibiotic resistance in waste water has increased tremendously in the past few years with advances in the molecular methods available. However, there are still some gaps in our knowledge on the subject, such as how active is horizontal gene transfer in waste water and what is the role of the waste water treatment plant in the environmental resistome? The purpose of this review is to briefly describe some of the main methods for studying antibiotic resistance in waste waters and the latest research and main knowledge gaps on the issue. In addition, some future research directions are proposed.

  • Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-30
    William H. Bowen, Robert A. Burne, Hui Wu, Hyun Koo

    Biofilms are microbial communities embedded within an extracellular matrix, forming a highly organized structure that causes many human infections. Dental caries (tooth decay) is a polymicrobial biofilm disease driven by the diet and microbiota–matrix interactions that occur on a solid surface. Sugars fuel the emergence of pathogens, the assembly of the matrix, and the acidification of the biofilm microenvironment, promoting ecological changes and concerted multispecies efforts that are conducive to acid damage of the mineralized tooth tissue. Here, we discuss recent advances in the role of the biofilm matrix and interactions between opportunistic pathogens and commensals in the pathogenesis of dental caries. In addition, we highlight the importance of matrix-producing organisms in fostering a pathogenic habitat where interspecies competition and synergies occur to drive the disease process, which could have implications to other infections associated with polymicrobial biofilms.

  • Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-21
    Laurie Pinaud, Philippe J. Sansonetti, Armelle Phalipon

    Microbial pathogens possess a diversity of weapons that disrupt host homeostasis and immune defenses, thus resulting in the establishment of infection. The best-characterized system mediating bacterial protein delivery into target eukaryotic cells is the type III secretion system (T3SS) expressed by Gram-negative bacteria, including the human enteric pathogens Shigella, Salmonella, Yersinia, and enteropathogenic/enterohemorragic Escherichia coli (EPEC/EHEC). The emerging global view is that these T3SS-bearing pathogens share similarities in their ability to target key cellular pathways such as the cell cytoskeleton, trafficking, cell death/survival, and the NF-κB and MAPK signaling pathways. In particular, multiple host proteins are targeted in a given pathway, and different T3SS effectors from various pathogens share functional similarities.

  • The New Kid on the Block: A Specialized Secretion System during Bacterial Sporulation
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-20
    Cécile Morlot, Christopher D.A. Rodrigues

    The transport of proteins across the bacterial cell envelope is mediated by protein complexes called specialized secretion systems. These nanomachines exist in both Gram-positive and Gram-negative bacteria and have been categorized into different types based on their structural components and function. Interestingly, multiple studies suggest the existence of a protein complex in endospore-forming bacteria that appears to be a new type of specialized secretion system. This protein complex is called the SpoIIIA-SpoIIQ complex and is an exception to the categorical norm since it appears to be a hybrid composed of different parts from well-defined specialized secretion systems. Here we summarize and discuss the current understanding of this complex and its potential role as a specialized secretion system.

  • Current Trends in Methylotrophy
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-19
    Ludmila Chistoserdova, Marina G. Kalyuzhnaya

    Methylotrophy is a field of study dealing with microorganisms capable of utilization of compounds devoid of carbon–carbon bonds (C1 compounds). In this review, we highlight several emerging trends in methylotrophy. First, we discuss the significance of the recent discovery of lanthanide-dependent alcohol dehydrogenases for understanding both the occurrence and the distribution of methylotrophy functions among bacteria, and then we discuss the newly appreciated role of lanthanides in biology. Next, we describe the detection of other methylotrophy pathways across novel bacterial taxa and insights into the evolution of methylotrophy. Further, data are presented on the occurrence and activity of aerobic methylotrophs in hypoxic and anoxic environments, questioning the prior assumptions on niche separation of aerobic and anaerobic methylotrophy. The concept of communal function in aerobic methane oxidation is also briefly discussed. Finally, we review recent research in engineering methylotrophs for biotechnological applications as well as recent progress in engineering synthetic methylotrophy.

  • Phasevarions of Bacterial Pathogens: Methylomics Sheds New Light on Old Enemies
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-13
    John M. Atack, Aimee Tan, Lauren O. Bakaletz, Michael P. Jennings, Kate L. Seib

    A wide variety of bacterial pathogens express phase-variable DNA methyltransferases that control expression of multiple genes via epigenetic mechanisms. These randomly switching regulons – phasevarions – regulate genes involved in pathogenesis, host adaptation, and antibiotic resistance. Individual phase-variable genes can be identified in silico as they contain easily recognized features such as simple sequence repeats (SSRs) or inverted repeats (IRs) that mediate the random switching of expression. Conversely, phasevarion-controlled genes do not contain any easily identifiable features. The study of DNA methyltransferase specificity using Single-Molecule, Real-Time (SMRT) sequencing and methylome analysis has rapidly advanced the analysis of phasevarions by allowing methylomics to be combined with whole-transcriptome/proteome analysis to comprehensively characterize these systems in a number of important bacterial pathogens.

  • Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-13
    Alex Hopke, Alistair J.P. Brown, Rebecca A. Hall, Robert T. Wheeler

    Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity.

  • The Archaellum: An Update on the Unique Archaeal Motility Structure
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-13
    Sonja-Verena Albers, Ken F. Jarrell

    Each of the three domains of life exhibits a unique motility structure: while Bacteria use flagella, Eukarya employ cilia, and Archaea swim using archaella. Since the new name for the archaeal motility structure was proposed, in 2012, a significant amount of new data on the regulation of transcription of archaella operons, the structure and function of archaellum subunits, their interactions, and cryo-EM data on in situ archaellum complexes in whole cells have been obtained. These data support the notion that the archaellum is evolutionary and structurally unrelated to the flagellum, but instead is related to archaeal and bacterial type IV pili and emphasize that it is a motility structure unique to the Archaea.

  • Antibacterial Weapons: Targeted Destruction in the Microbiota
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-13
    Benoit Chassaing, Eric Cascales

    The intestinal microbiota plays an important role in health, particularly in promoting intestinal metabolic capacity and in maturing the immune system. The intestinal microbiota also mediates colonization resistance against pathogenic bacteria, hence protecting the host from infections. In addition, some bacterial pathogens deliver toxins that target phylogenetically related or distinct bacterial species in order to outcompete and establish within the microbiota. The most widely distributed weapons include bacteriocins, as well as contact-dependent growth inhibition and type VI secretion systems. In this review, we discuss important advances about the impact of such antibacterial systems on shaping the intestinal microbiota.

  • Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-10
    Paulo Durão, Roberto Balbontín, Isabel Gordo

    Antibiotics target essential cellular functions but bacteria can become resistant by acquiring either exogenous resistance genes or chromosomal mutations. Resistance mutations typically occur in genes encoding essential functions; these mutations are therefore generally detrimental in the absence of drugs. However, bacteria can reduce this handicap by acquiring additional mutations, known as compensatory mutations. Genetic interactions (epistasis) either with the background or between resistances (in multiresistant bacteria) dramatically affect the fitness cost of antibiotic resistance and its compensation, therefore shaping dissemination of antibiotic resistance mutations. This Review summarizes current knowledge on the evolutionary mechanisms influencing maintenance of resistance mediated by chromosomal mutations, focusing on their fitness cost, compensatory evolution, epistasis, and the effect of the environment on these processes.

  • Life on Phosphite: A Metagenomics Tale
    Trends Microbiol. (IF 11.02) Pub Date : 2018-02-03
    Yunuen Tapia-Torres, Gabriela Olmedo-Álvarez

    Phosphite, a species of phosphorus in a P3+ oxidation state, is believed to have played an important role in the primordial Earth. Figueroa et al. used metagenomics to uncover anaerobic bacterial communities from waste water waste sludge that sustain life from energy provided by phosphite.

  • Infection’s Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-24
    Steven L. Taylor, Michael A. McGuckin, Steve Wesselingh, Geraint B. Rogers

    Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host–pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy.

  • In Silico Vaccine Strain Prediction for Human Influenza Viruses
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-09
    Thorsten R. Klingen, Susanne Reimering, Carlos A. Guzmán, Alice C. McHardy

    Vaccines preventing seasonal influenza infections save many lives every year; however, due to rapid viral evolution, they have to be updated frequently to remain effective. To identify appropriate vaccine strains, the World Health Organization (WHO) operates a global program that continually generates and interprets surveillance data. Over the past decade, sophisticated computational techniques, drawing from multiple theoretical disciplines, have been developed that predict viral lineages rising to predominance, assess their suitability as vaccine strains, link genetic to antigenic alterations, as well as integrate and visualize genetic, epidemiological, structural, and antigenic data. These could form the basis of an objective and reproducible vaccine strain-selection procedure utilizing the complex, large-scale data types from surveillance. To this end, computational techniques should already be incorporated into the vaccine-selection process in an independent, parallel track, and their performance continuously evaluated.

  • 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.

  • 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.

  • 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.

  • Antiviral Immunity and Virus-Mediated Antagonism in Disease Vector Mosquitoes
    Trends Microbiol. (IF 11.02) Pub Date : 2018-01-31
    Glady Hazitha Samuel, Zach N. Adelman, Kevin M. Myles

    More than 100 pathogens, spanning multiple virus families, broadly termed ‘arthropod-borne viruses (arboviruses)’ have been associated with human and/or animal diseases. These viruses persist in nature through transmission cycles that involve alternating replication in susceptible vertebrate and invertebrate hosts. Collectively, these viruses are among the greatest burdens to global health, due to their widespread prevalence, and the severe morbidity and mortality they cause in human and animal hosts. Specific examples of mosquito-borne pathogens include Zika virus (ZIKV), West Nile virus (WNV), dengue virus serotypes 1–4 (DENV 1–4), Japanese encephalitis virus (JEV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Interactions between arboviruses and the immune pathways of vertebrate hosts have been extensively reviewed. In this review we focus on the antiviral immune pathways present in mosquitoes. We also discuss mechanisms by which mosquito-borne viruses may antagonize antiviral pathways in disease vectors. Finally, we elaborate on the possibility that mosquito-borne viruses may be engaged in an evolutionary arms race with their invertebrate vector hosts, and the possible implications of this for understanding the transmission of mosquito-borne viruses.

  • Legionella Effectors Explored with INSeq: New Functional Insights
    Trends Microbiol. (IF 11.02) Pub Date : 2018-01-31
    Monica Rolando, Carmen Buchrieser

    Legionella pneumophila secretes over 300 effector proteins that manipulate host cells. This multiplicity of effectors hampers the characterization of their individual roles. Shames et al. report a new approach to solve the enigma of Legionella effector function by using INSeq to analyse effector functions in the context of infection.

  • Rise of a Cereal Killer: The Biology of Magnaporthe oryzae Biotrophic Growth
    Trends Microbiol. (IF 11.02) Pub Date : 2018-01-24
    Jessie Fernandez, Kim Orth

    The rice blast fungus, Magnaporthe oryzae, causes one of the most destructive diseases of cultivated rice in the world. Infections caused by this recalcitrant pathogen lead to the annual destruction of approximately 10–30% of the rice harvested globally. The fungus undergoes extensive developmental changes to be able to break into plant cells, build elaborate infection structures, and proliferate inside host cells without causing visible disease symptoms. From a molecular standpoint, we are still in the infancy of understanding how M. oryzae manipulates the host during this complex multifaceted infection. Here, we describe recent advances in our understanding of the cell biology of M. oryzae biotrophic interaction and key molecular factors required for the disease establishment in rice cells.

  • Immunomodulatory Nonstructural Proteins of Influenza A Viruses
    Trends Microbiol. (IF 11.02) Pub Date : 2018-01-17
    Carolin Klemm, Yvonne Boergeling, Stephan Ludwig, Christina Ehrhardt

    Influenza epidemics and pandemics still represent a severe public health threat and cause significant morbidity and mortality worldwide. As intracellular parasites, influenza viruses are strongly dependent on the host cell machinery. To ensure efficient production of progeny viruses, viral proteins extensively interfere with cellular signalling pathways to inhibit antiviral responses or to activate virus-supportive functions. Here, we review various functions of the influenza virus nonstructural proteins NS1, PB1-F2, and PA-X in infected cells and how post-transcriptional modifications of these proteins affect the viral life cycle. Furthermore, we discuss newly discovered interactions between these proteins and the antiviral interferon response.

  • Turning Over a New Leaf: Bacteriocins Going Green
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-14
    Maarten G.K. Ghequire, René De Mot

    Bacteriocins are potent antibacterial proteins that selectively kill phylogenetic relatives of the producer. Their polymorphic nature, most prominent in γ-Proteobacteria, offers potential for the design of customized bacteriocin cocktails targeting Gram-negative pathogens. As an alternative to recombinant production in bacteria, they are eligible for large-scale production in plants.

  • Antibiotic Killing through Incomplete DNA Repair
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-17
    Benno H. ter Kuile, Marloes Hoeksema

    Two recent studies show that incomplete repair of DNA damage due to oxidized nucleotides is crucial for reactive oxygen species (ROS)-related antimicrobial lethality. Using widely different experimental approaches they both reach the same conclusions on the role of downstream ROS production in cell killing upon exposure to bactericidal antimicrobials.

  • Transmissible Viral Vaccines
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-13
    James J. Bull, Mark W. Smithson, Scott L. Nuismer

    Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution. Approaches that integrate vaccine engineering with an understanding of evolution and epidemiology will reap the greatest benefit from vaccine transmission.

  • 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.

  • 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.

  • 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.

  • 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.

  • Small RNA, Big Effect: Control of Flagellin Production
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-30
    Aleksandra A. Miranda-CasoLuengo, Stefani C. Kary, Marc Erhardt, Carsten Kröger

    Many bacteria move in their environment using a remarkable, rotating nanomachine – the flagellum. In a recent publication, Choi et al. report a new addition to the group of flagellar regulators, a trans-acting small RNA (sRNA).

  • Anti-HIV Passive Immunization: New Weapons in the Arsenal
    Trends Microbiol. (IF 11.02) Pub Date : 2017-10-30
    Ruth M. Ruprecht

    Anti-HIV passive immunization with human neutralizing monoclonal antibodies (nmAbs) has made exciting gains: (i) identification of the HIV envelope V2 apex as a new in vivo protective epitope, (ii) a novel clade C SHIV for challenge studies, and (iii) a highly protective, trispecific nmAb. Potent, broad-spectrum protection by nmAbs holds promise.

  • 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.

  • 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.

  • 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.

  • 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.

  • The Role of Interferon in Persistent Viral Infection: Insights from Murine Norovirus
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-17
    Timothy J. Nice, Bridget A. Robinson, Jacob A. Van Winkle

    Persistent viral infections result from evasion or avoidance of sterilizing immunity, extend the timeframe of virus transmission, and can trigger disease. Prior studies in mouse models of persistent infection have suggested that ineffective adaptive immune responses are necessary for persistent viral infection. However, recent work in the murine norovirus (MNV) model of persistent infection demonstrates that innate immunity can control both early and persistent viral replication independently of adaptive immune effector functions. Interferons (IFNs) are central to the innate control of persistent MNV, apart from a role in modulating adaptive immunity. Furthermore, subtypes of IFN play distinct tissue-specific roles in innate control of persistent MNV infection. Type I IFN (IFN-α/β) controls systemic replication, and type III IFN (IFN-λ) controls MNV persistence in the intestinal epithelium. In this article, we review recent findings in the MNV model, highlighting the role of IFNs and innate immunity in clearing persistent viral infection, and discussing the broader implications of these findings for control of persistent human infections.

  • Not Just Antibiotics: Is Cancer Chemotherapy Driving Antimicrobial Resistance?
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-13
    Lito E. Papanicolas, David L. Gordon, Steve L. Wesselingh, Geraint B. Rogers

    The global spread of antibiotic-resistant pathogens threatens to increase the mortality of cancer patients significantly. We propose that chemotherapy contributes to the emergence of antibiotic-resistant bacteria within the gut and, in combination with antibiotics, drives pathogen overgrowth and translocation into the bloodstream. In our model, these processes are mediated by the effects of chemotherapy on bacterial mutagenesis and horizontal gene transfer, the disruption of commensal gut microbiology, and alterations to host physiology. Clinically, this model manifests as a cycle of recurrent sepsis, with each episode involving ever more resistant organisms and requiring increasingly broad-spectrum antimicrobial therapy. Therapies that restore the gut microbiota following chemotherapy or antibiotics could provide a means to break this cycle of infection and treatment failure.

  • Quorum-Sensing Systems as Targets for Antivirulence Therapy
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-10
    Tom Defoirdt

    The development of novel therapies to control diseases caused by antibiotic-resistant pathogens is one of the major challenges we are currently facing. Many important plant, animal, and human pathogens regulate virulence by quorum sensing, bacterial cell-to-cell communication with small signal molecules. Consequently, a significant research effort is being undertaken to identify and use quorum-sensing-interfering agents in order to control diseases caused by these pathogens. In this review, an overview of our current knowledge of quorum-sensing systems of Gram-negative model pathogens is presented as well as the link with virulence of these pathogens, and recent advances and challenges in the development of quorum-sensing-interfering therapies are discussed.

  • A Tale of Two Viruses: Does Heterologous Flavivirus Immunity Enhance Zika Disease?
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-06
    Carlos A. Sariol, Mauricio L. Nogueira, Nikos Vasilakis

    The rise of Zika virus (ZIKV) and its unusual clinical manifestations provided ground for speculative debate. The clinical severity of secondary dengue virus (DENV) infections is associated with antibody-dependent enhancement (ADE), and it was recently suggested that previous exposure to DENV may worsen ZIKV clinical outcomes. In this Opinion article we analyze the relationship among different flaviviruses and ADE. We discuss new evidence obtained in non-human primates and human cohorts demonstrating that there is no correlation to ADE when ZIKV infection occurs in the presence of pre-existing DENV immunity. We propose a redefinition of ADE in the context of complex immunological flavivirus interactions to provide a more objective perspective when translating in vitro or in vivo observations into the clinical setting.

  • A Call to Arms: Quest for a Cryptococcal Vaccine
    Trends Microbiol. (IF 11.02) Pub Date : 2017-11-02
    Marley C. Caballero Van Dyke, Floyd L. Wormley

    Cryptococcosis remains a significant cause of morbidity and mortality world-wide, particularly among AIDS patients. Yet, to date, there are no licensed vaccines clinically available to treat or prevent cryptococcosis. In this review, we provide a rationale to support continued investment in Cryptococcus vaccine research, potential challenges that must be overcome along the way, and a literature review of the current progress underway towards developing a vaccine to prevent cryptococcosis.

  • Personalized Medicine and Infectious Disease Management
    Trends Microbiol. (IF 11.02) Pub Date : 2017-09-29
    Slade O. Jensen, Sebastiaan J. van Hal

    A recent study identified pathogen factors associated with an increased mortality risk in Staphylococcus aureus bacteremia, using predictive modelling and a combination of genotypic, phenotypic, and clinical data. This study conceptually validates the benefit of personalized medicine and highlights the potential use of whole genome sequencing in infectious disease management.

  • Roles of Endogenous Retroviruses in Early Life Events
    Trends Microbiol. (IF 11.02) Pub Date : 2017-09-29
    Gkikas Magiorkinis, Aris Katzourakis, Pagona Lagiou

    A retrovirus that infected our ancestors 100 million years ago became a human gene that is expressed in embryos and cancers, and can be detected in the blood of pregnant women. Accumulating evidence suggests potential roles for endogenous retroviruses in early life events, which may affect adult health.

  • 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.

  • Transfer of Antibiotic Resistance in Staphylococcus aureus
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-20
    Jakob Haaber, José R. Penadés, Hanne Ingmer

    Staphylococcus aureus is a serious human pathogen with remarkable adaptive powers. Antibiotic-resistant clones rapidly emerge mainly by acquisition of antibiotic-resistance genes from other S. aureus strains or even from other genera. Transfer is mediated by a diverse complement of mobile genetic elements and occurs primarily by conjugation or bacteriophage transduction, with the latter traditionally being perceived as the primary route. Recent work on conjugation and transduction suggests that transfer by these mechanisms may be more extensive than previously thought, in terms of the range of plasmids that can be transferred by conjugation and the efficiency with which transduction occurs. Here, we review the main routes of antibiotic resistance gene transfer in S. aureus in the context of its biology as a human commensal and a life-threatening pathogen.

  • The Emerging Roles of STING in Bacterial Infections
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-15
    Fabio V. Marinho, Sulayman Benmerzoug, Sergio C. Oliveira, Bernhard Ryffel, V.F.J. Quesniaux

    The STING (Stimulator of Interferon Genes) protein connects microorganism cytosolic sensing with effector functions of the host cell by sensing directly cyclic dinucleotides (CDNs), originating from pathogens or from the host upon DNA recognition. Although STING activation favors effective immune responses against viral infections, its role during bacterial diseases is controversial, ranging from protective to detrimental effects for the host. In this review, we summarize important features of the STING activation pathway and recent highlights about the role of STING in bacterial infections by Chlamydia, Listeria, Francisella, Brucella, Shigella, Salmonella, Streptococcus, and Neisseria genera, with a special focus on mycobacteria.

  • Perinatal Group B Streptococcal Infections: Virulence Factors, Immunity, and Prevention Strategies
    Trends Microbiol. (IF 11.02) Pub Date : 2017-06-17
    Jay Vornhagen, Kristina M. Adams Waldorf, Lakshmi Rajagopal

    Group B streptococcus (GBS) or Streptococcus agalactiae is a β-hemolytic, Gram-positive bacterium that is a leading cause of neonatal infections. GBS commonly colonizes the lower gastrointestinal and genital tracts and, during pregnancy, neonates are at risk of infection. Although intrapartum antibiotic prophylaxis during labor and delivery has decreased the incidence of early-onset neonatal infection, these measures do not prevent ascending infection that can occur earlier in pregnancy leading to preterm births, stillbirths, or late-onset neonatal infections. Prevention of GBS infection in pregnancy is complex and is likely influenced by multiple factors, including pathogenicity, host factors, vaginal microbiome, false-negative screening, and/or changes in antibiotic resistance. A deeper understanding of the mechanisms of GBS infections during pregnancy will facilitate the development of novel therapeutics and vaccines. Here, we summarize and discuss important advancements in our understanding of GBS vaginal colonization, ascending infection, and preterm birth.

  • 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.
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