Showing papers in "Nature Reviews Microbiology in 2015"
TL;DR: Recent advances in understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics are reviewed, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
Abstract: Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.
2,837 citations
TL;DR: How basic science studies are elucidating the molecular details of the crosstalk that occurs at the host–pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs is discussed.
Abstract: Urinary tract infections (UTIs) are a severe public health problem and are caused by a range of pathogens, but most commonly by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus. High recurrence rates and increasing antimicrobial resistance among uropathogens threaten to greatly increase the economic burden of these infections. In this Review, we discuss how basic science studies are elucidating the molecular details of the crosstalk that occurs at the host-pathogen interface, as well as the consequences of these interactions for the pathophysiology of UTIs. We also describe current efforts to translate this knowledge into new clinical treatments for UTIs.
2,251 citations
TL;DR: An approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR–cas loci into distinct classes, types and subtypes is presented.
Abstract: The evolution of CRISPR-cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR-cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR-Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.
1,988 citations
Dresden University of Technology1, Catholic University of Portugal2, Centre national de la recherche scientifique3, University of Cyprus4, Agricultural Research Organization, Volcani Center5, Maynooth University6, Swiss Federal Institute of Aquatic Science and Technology7, Norwegian University of Life Sciences8, University of Lorraine9, Vienna University of Technology10, University of Turku11, University of Catania12, Karlsruhe Institute of Technology13, University of Tartu14, Cajal Institute15, Spanish National Research Council16
TL;DR: The main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment are discussed.
Abstract: Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.
1,495 citations
TL;DR: This Review discusses recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles.
Abstract: In this Review, Schwechheimer and Kuehn describe recent developments in elucidating the mechanisms of biogenesis and cargo selection of the outer-membrane vesicles (OMVs) produced by Gram-negative bacteria. They also discuss the functions of OMVs in bacterial physiology and during pathogenesis. Outer-membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content and are commonly produced by Gram-negative bacteria. The production of OMVs allows bacteria to interact with their environment, and OMVs have been found to mediate diverse functions, including promoting pathogenesis, enabling bacterial survival during stress conditions and regulating microbial interactions within bacterial communities. Additionally, because of this functional versatility, researchers have begun to explore OMVs as a platform for bioengineering applications. In this Review, we discuss recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles.
1,090 citations
TL;DR: The current status of vesiculogenesis research in thick-walled microorganisms is described and the cargo and functions associated with EVs in these species are discussed.
Abstract: Extracellular vesicles (EVs) are produced by all domains of life In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown Nonetheless, EVs have been described in a variety of cell-walled organisms, including Staphylococcus aureus, Mycobacterium tuberculosis and Cryptococcus neoformans These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes, and have important roles in microbial physiology and pathogenesis In this Review, we describe the current status of vesiculogenesis research in thick-walled microorganisms and discuss the cargo and functions associated with EVs in these species
834 citations
TL;DR: The ecology of rare microbial populations is discussed, molecular and computational methods for targeting taxonomic 'blind spots' within the rare biosphere of complex microbial communities are highlighted, and the value of studying the biogeography of microorganisms is highlighted.
Abstract: The profound influence of microorganisms on human life and global biogeochemical cycles underlines the value of studying the biogeography of microorganisms, exploring microbial genomes and expanding our understanding of most microbial species on Earth: that is, those present at low relative abundance. The detection and subsequent analysis of low-abundance microbial populations—the 'rare biosphere'—have demonstrated the persistence, population dynamics, dispersion and predation of these microbial species. We discuss the ecology of rare microbial populations, and highlight molecular and computational methods for targeting taxonomic 'blind spots' within the rare biosphere of complex microbial communities.
794 citations
TL;DR: The structural and mechanistic relationships between these single- and double-membrane-embedded systems are explored, and how this knowledge can be exploited for the development of new antimicrobial strategies are discussed.
Abstract: Bacteria have evolved a remarkable array of sophisticated nanomachines to export various virulence factors across the bacterial cell envelope. In recent years, considerable progress has been made towards elucidating the structural and molecular mechanisms of the six secretion systems (types I-VI) of Gram-negative bacteria, the unique mycobacterial type VII secretion system, the chaperone-usher pathway and the curli secretion machinery. These advances have greatly enhanced our understanding of the complex mechanisms that these macromolecular structures use to deliver proteins and DNA into the extracellular environment or into target cells. In this Review, we explore the structural and mechanistic relationships between these single- and double-membrane-embedded systems, and we briefly discuss how this knowledge can be exploited for the development of new antimicrobial strategies.
792 citations
TL;DR: This Review discusses the strategies that have been developed in bacteria and fungi to identify and induce the expression of silent BGCs, and briefly summarize methods for the isolation and structural characterization of their metabolic products.
Abstract: Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities and a wide variety of applications in medicine and agriculture, such as the treatment of infectious diseases and cancer, and the prevention of crop damage. Genomics has revealed that many microorganisms have far greater potential to produce specialized metabolites than was thought from classic bioactivity screens; however, realizing this potential has been hampered by the fact that many specialized metabolite biosynthetic gene clusters (BGCs) are not expressed in laboratory cultures. In this Review, we discuss the strategies that have been developed in bacteria and fungi to identify and induce the expression of such silent BGCs, and we briefly summarize methods for the isolation and structural characterization of their metabolic products.
692 citations
TL;DR: Rules are proposed for estimating the risks associated with genes that are present in environmental resistomes by evaluating the likelihood of their introduction into human pathogens, and the consequences of such events for the treatment of infections.
Abstract: In this Opinion article, Baquero and colleagues propose a hierarchical system for estimating the risks associated with genes present in environmental resistomes, by evaluating the likelihood of their introduction into human pathogens, and the consequences of such introduction events for the treatment of bacterial infections.
679 citations
TL;DR: How phenotypic heterogeneity allows genotypes to persist in fluctuating environments is discussed and how it promotes interactions between Phenotypic subpopulations in clonal groups, providing microbial groups with new functionality is described.
Abstract: Most microbial communities consist of a genetically diverse assembly of different organisms, and the level of genetic diversity plays an important part in community properties and functions. However, biological diversity also arises at a lower level of biological organization, between genetically identical cells that reside in the same microenvironment. In this Review, I outline the molecular mechanisms responsible for phenotypic heterogeneity and discuss how phenotypic heterogeneity allows genotypes to persist in fluctuating environments. I also describe how it promotes interactions between phenotypic subpopulations in clonal groups, providing microbial groups with new functionality.
TL;DR: This Review summarizes recent insights on the molecular mechanisms governing the activity of the RelA/SpoT homologue (RSH) proteins, which are key players that regulate the cellular levels of (p)ppGpp.
Abstract: The alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p) ppGpp) are involved in regulating growth and several different stress responses in bacteria. In ...
TL;DR: In this paper, the authors discuss emerging strategies for microbial community analysis that complement and expand traditional metagenomic profiling, such as novel DNA sequencing strategies for identifying strain-level microbial variation and community temporal dynamics; measuring multiple 'omic' data types that better capture community functional activity; and combining multiple forms of omic data in an integrated framework.
Abstract: High-throughput DNA sequencing has proven invaluable for investigating diverse environmental and host-associated microbial communities. In this Review, we discuss emerging strategies for microbial community analysis that complement and expand traditional metagenomic profiling. These include novel DNA sequencing strategies for identifying strain-level microbial variation and community temporal dynamics; measuring multiple 'omic' data types that better capture community functional activity, such as transcriptomics, proteomics and metabolomics; and combining multiple forms of omic data in an integrated framework. We highlight studies in which the 'multi-omics' approach has led to improved mechanistic models of microbial community structure and function.
TL;DR: This Review summarizes the current understanding of marine microbial community dynamics at various scales, from hours to decades, and explains how the data illustrate community resilience and seasonality, and reveal interactions among microorganisms.
Abstract: Recent advances in studying the dynamics of marine microbial communities have shown that the composition of these communities follows predictable patterns and involves complex network interactions, which shed light on the underlying processes regulating these globally important organisms. Such 'holistic' (or organism- and system-based) studies of these communities complement popular reductionist, often culture-based, approaches for understanding organism function one gene or protein at a time. In this Review, we summarize our current understanding of marine microbial community dynamics at various scales, from hours to decades. We also explain how the data illustrate community resilience and seasonality, and reveal interactions among microorganisms.
TL;DR: This Review highlights recent progress in elucidating the late stages of the HIV-1 replication cycle and the related interplay between virology, cell and molecular biology, and drug discovery.
Abstract: In this article, Eric Freed reviews recent progress in elucidating the steps involved in HIV-1 assembly, release and maturation, highlighting how these events are orchestrated by the viral Gag precursor protein and how this information is being used to develop novel anti-HIV-1 therapeutics. Major advances have occurred in recent years in our understanding of HIV-1 assembly, release and maturation, as work in this field has been propelled forwards by developments in imaging technology, structural biology, and cell and molecular biology. This increase in basic knowledge is being applied to the development of novel inhibitors designed to target various aspects of virus assembly and maturation. This Review highlights recent progress in elucidating the late stages of the HIV-1 replication cycle and the related interplay between virology, cell and molecular biology, and drug discovery.
TL;DR: A century of phage research is discussed and its impact on basic and applied biology is discussed, from sequencing and genome engineering to the recent discovery and exploitation of CRISPR–Cas phage resistance systems.
Abstract: Phages were discovered 100 years ago, and since then phage research has transformed fundamental and translational biosciences. In this Timeline, Salmond and Fineran discuss a century of phage research, describing the roles of phages in ecosystems and in driving bacterial evolution and virulence, and highlight their impact as a source of novel reagents that revolutionized molecular biology and biotechnology. Viruses that infect bacteria (bacteriophages; also known as phages) were discovered 100 years ago. Since then, phage research has transformed fundamental and translational biosciences. For example, phages were crucial in establishing the central dogma of molecular biology — information is sequentially passed from DNA to RNA to proteins — and they have been shown to have major roles in ecosystems, and help drive bacterial evolution and virulence. Furthermore, phage research has provided many techniques and reagents that underpin modern biology — from sequencing and genome engineering to the recent discovery and exploitation of CRISPR–Cas phage resistance systems. In this Timeline, we discuss a century of phage research and its impact on basic and applied biology.
TL;DR: Prochlorococcus is seen as a 'federation' of diverse cells that sustains its broad distribution, stability and abundance in the oceans via extensive genomic and phenotypic diversity and is proving to be a useful model system for elucidating the forces that shape microbial populations and ecosystems.
Abstract: The marine cyanobacteriumProchlorococcusis the most abundant photosynthetic organism on earth. In this Review, Chisholm and colleagues highlight the enormous genomic diversity of this phototroph, discuss the factors that contribute to this diversity and consider its ecological consequences. The marine cyanobacterium Prochlorococcus is the smallest and most abundant photosynthetic organism on Earth. In this Review, we summarize our understanding of the diversity of this remarkable phototroph and describe its role in ocean ecosystems. We discuss the importance of interactions of Prochlorococcus with the physical environment, with phages and with heterotrophs in shaping the ecology and evolution of this group. In light of recent studies, we have come to view Prochlorococcus as a 'federation' of diverse cells that sustains its broad distribution, stability and abundance in the oceans via extensive genomic and phenotypic diversity. Thus, it is proving to be a useful model system for elucidating the forces that shape microbial populations and ecosystems.
TL;DR: This Review highlights how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B cell and T cell responses, and discusses how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S.Aureus.
Abstract: Staphylococcus aureus, a bacterial commensal of the human nares and skin, is a frequent cause of soft tissue and bloodstream infections. A hallmark of staphylococcal infections is their frequent recurrence, even when treated with antibiotics and surgical intervention, which demonstrates the bacterium's ability to manipulate innate and adaptive immune responses. In this Review, we highlight how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B cell and T cell responses, and we discuss how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S. aureus.
TL;DR: Current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts is summarized, with a particular focus on Salmonella enterica subsp.
Abstract: Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms that salmonellae use to alter host cell physiology; through the delivery of effector proteins with specific activities and through the modulation of defence and stress response pathways. In this Review, we summarize our current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts, with a particular focus on Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps in our knowledge of the contributions of salmonellae and the host to disease pathogenesis, and we suggest future avenues for further study.
TL;DR: Understanding of the interactions between the viral capsid core and several cellular factors that enable efficient HIV-1 genome replication, timely core disassembly, nuclear import and the integration of the viral genome into the genome of the target cell are described.
Abstract: In a mature, infectious HIV-1 virion, the viral genome is housed within a conical capsid core made from the viral capsid (CA) protein. The CA protein and the structure into which it assembles facilitate virtually every step of infection through a series of interactions with multiple host cell factors. This Review describes our understanding of the interactions between the viral capsid core and several cellular factors that enable efficient HIV-1 genome replication, timely core disassembly, nuclear import and the integration of the viral genome into the genome of the target cell. We then discuss how elucidating these interactions can reveal new targets for therapeutic interactions against HIV-1.
TL;DR: Another type of bacterium–phage interaction is discussed, active lysogeny, in which phages or phage-like elements are integrated into the bacterial chromosome within critical genes or operons and serve as switches that regulate bacterial genes via genome excision.
Abstract: Unlike lytic phages, temperate phages that enter lysogeny maintain a long-term association with their bacterial host. In this context, mutually beneficial interactions can evolve that support efficient reproduction of both phages and bacteria. Temperate phages are integrated into the bacterial chromosome as large DNA insertions that can disrupt gene expression, and they may pose a fitness burden on the cell. However, they have also been shown to benefit their bacterial hosts by providing new functions in a bacterium-phage symbiotic interaction termed lysogenic conversion. In this Opinion article, we discuss another type of bacterium-phage interaction, active lysogeny, in which phages or phage-like elements are integrated into the bacterial chromosome within critical genes or operons and serve as switches that regulate bacterial genes via genome excision.
TL;DR: This Review discusses current knowledge about vRNP trafficking within host cells and the function of these complexes in the context of the virus life cycle, highlighting how structure contributes to function and the crucial interactions with host cell pathways, as well as on the information gaps that remain.
Abstract: Influenza A viral ribonucleoprotein (vRNP) complexes comprise the eight genomic negative-sense RNAs, each of which is bound to multiple copies of the vRNP and a trimeric viral polymerase complex. The influenza virus life cycle centres on the vRNPs, which in turn rely on host cellular processes to carry out functions that are necessary for the successful completion of the virus life cycle. In this Review, we discuss our current knowledge about vRNP trafficking within host cells and the function of these complexes in the context of the virus life cycle, highlighting how structure contributes to function and the crucial interactions with host cell pathways, as well as on the information gaps that remain. An improved understanding of how vRNPs use host cell pathways is essential to identify mechanisms of virus pathogenicity, host adaptation and, ultimately, new targets for antiviral intervention.
TL;DR: This Review discusses V. cholerae surface attachment, various matrix components and the regulatory networks controlling biofilm formation in this model organism that spends much of its life cycle outside of the human host in the aquatic environment.
Abstract: Nearly all bacteria form biofilms as a strategy for survival and persistence. Biofilms are associated with biotic and abiotic surfaces and are composed of aggregates of cells that are encased by a self-produced or acquired extracellular matrix. Vibrio cholerae has been studied as a model organism for understanding biofilm formation in environmental pathogens, as it spends much of its life cycle outside of the human host in the aquatic environment. Given the important role of biofilm formation in the V. cholerae life cycle, the molecular mechanisms underlying this process and the signals that trigger biofilm assembly or dispersal have been areas of intense investigation over the past 20 years. In this Review, we discuss V. cholerae surface attachment, various matrix components and the regulatory networks controlling biofilm formation.
TL;DR: This Review summarizes current knowledge of the microbial ecology of frozen waters, including the diversity of niches, the composition of microbial communities at these sites and their biogeochemical activities.
Abstract: The Earth's cryosphere comprises those regions that are cold enough for water to turn into ice. Recent findings show that the icy realms of polar oceans, glaciers and ice sheets are inhabited by microorganisms of all three domains of life, and that temperatures below 0 °C are an integral force in the diversification of microbial life. Cold-adapted microorganisms maintain key ecological functions in icy habitats: where sunlight penetrates the ice, photoautotrophy is the basis for complex food webs, whereas in dark subglacial habitats, chemoautotrophy reigns. This Review summarizes current knowledge of the microbial ecology of frozen waters, including the diversity of niches, the composition of microbial communities at these sites and their biogeochemical activities.
TL;DR: Recent technological advances in marine virology including the use of near-quantitative, reproducible metagenomics for large-scale investigation of viral communities and the emergence of gene-based viral ecology are discussed.
Abstract: Marine viruses have important roles in microbial mortality, gene transfer, metabolic reprogramming and biogeochemical cycling. In this Review, we discuss recent technological advances in marine virology including the use of near-quantitative, reproducible metagenomics for large-scale investigation of viral communities and the emergence of gene-based viral ecology. We also describe the reprogramming of microbially driven processes by viral metabolic genes, the identification of novel viruses using cultivation-dependent and cultivation-independent tools, and the potential for modelling studies to provide a framework for studying virus-host interactions. These transformative advances have set a rapid pace in exploring and predicting how marine viruses manipulate and respond to their environment.
TL;DR: The social history of sequencing is summarized and its impact on the authors' understanding of the biology, diversity and evolution of bacteria is summarized, while also highlighting spin-offs and translational impact in the clinic.
Abstract: Twenty years ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae, shook the world of bacteriology. In this Timeline, we review the first two decades of bacterial genome sequencing, which have been marked by three revolutions: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing. We summarize the social history of sequencing and its impact on our understanding of the biology, diversity and evolution of bacteria, while also highlighting spin-offs and translational impact in the clinic. We look forward to a 'sequencing singularity', where sequencing becomes the method of choice for as-yet unthinkable applications in bacteriology and beyond.
TL;DR: The evidence that IFNs can control HIV-1 replication in vivo is discussed and the controversial role of IFNs in promoting the pathological sequelae of chronic HIV- 1 infection is debated.
Abstract: The ability of interferons (IFNs) to inhibit HIV-1 replication in cell culture models has long been recognized, and the therapeutic administration of IFNα to HIV-1-infected patients who are not receiving antiretroviral therapy produces a clear but transient decrease in plasma viral load Conversely, studies of chronic HIV-1 infection in humans and SIV-infected animal models of AIDS show positive correlations between elevated plasma levels of IFNs, increased expression of IFN-stimulated genes (ISGs), biomarkers of inflammation and disease progression In this Review, we discuss the evidence that IFNs can control HIV-1 replication in vivo and debate the controversial role of IFNs in promoting the pathological sequelae of chronic HIV-1 infection
TL;DR: It is argued that an in-depth assessment of the impacts of dispersant on microorganisms is needed to evaluate the planning and use of dispersants during future responses to oil spills.
Abstract: Dispersants are globally and routinely applied as an emergency response to oil spills in marine ecosystems with the goal of chemically enhancing the dissolution of oil into water, which is assumed to stimulate microbially mediated oil biodegradation. However, little is known about how dispersants affect the composition of microbial communities or their biodegradation activities. The published findings are controversial, probably owing to variations in laboratory methods, the selected model organisms and the chemistry of different dispersant-oil mixtures. Here, we argue that an in-depth assessment of the impacts of dispersants on microorganisms is needed to evaluate the planning and use of dispersants during future responses to oil spills.
TL;DR: This work summarizes the current understanding of apoptotic mimicry as a mechanism for virus entry, binding and immune evasion and describes recent examples of non-enveloped viruses that use this mimicry strategy.
Abstract: As opportunistic pathogens, viruses have evolved many elegant strategies to manipulate host cells for infectious entry and replication. Viral apoptotic mimicry, defined by the exposure of phosphatidylserine - a marker for apoptosis - on the pathogen surface, is emerging as a common theme used by enveloped viruses to promote infection. Focusing on the four best described examples (vaccinia virus, dengue virus, Ebola virus and pseudotyped lentivirus), we summarize our current understanding of apoptotic mimicry as a mechanism for virus entry, binding and immune evasion. We also describe recent examples of non-enveloped viruses that use this mimicry strategy, and discuss future directions and how viral apoptotic mimicry could be targeted therapeutically.
TL;DR: This Opinion article considers conceptual challenges in the context of the current use of omics in soil microbiology, but the main arguments presented are also relevant to the application of omic to marine, freshwater, gut or other environments.
Abstract: Technological advances are enabling the sequencing of environmental DNA and RNA at increasing depth and with decreasing costs Metagenomic and transcriptomic analysis of soil microbial communities and the assembly of 'population genomes' from soil DNA are therefore now feasible Although the value of such 'omic' approaches is limited by the associated technical and bioinformatic difficulties, even if these obstacles were eliminated and 'perfect' metagenomes and metatranscriptomes were available, important conceptual challenges remain This Opinion article considers these conceptual challenges in the context of the current use of omics in soil microbiology, but the main arguments presented are also relevant to the application of omics to marine, freshwater, gut or other environments