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Showing papers in "Nature Reviews Microbiology in 2007"


Journal ArticleDOI
TL;DR: Viruses are by far the most abundant 'lifeforms' in the oceans and are the reservoir of most of the genetic diversity in the sea, thereby driving the evolution of both host and viral assemblages.
Abstract: If stretched end to end, the estimated 1030viruses in the oceans would span farther than the nearest 60 galaxies. This reservoir of genetic and biological diversity continues to yield exciting discoveries and, in this Review, Curtis A. Suttle highlights the areas that are likely to be of greatest interest in the next few years. Viruses are by far the most abundant 'lifeforms' in the oceans and are the reservoir of most of the genetic diversity in the sea. The estimated 1030 viruses in the ocean, if stretched end to end, would span farther than the nearest 60 galaxies. Every second, approximately 1023 viral infections occur in the ocean. These infections are a major source of mortality, and cause disease in a range of organisms, from shrimp to whales. As a result, viruses influence the composition of marine communities and are a major force behind biogeochemical cycles. Each infection has the potential to introduce new genetic information into an organism or progeny virus, thereby driving the evolution of both host and viral assemblages. Probing this vast reservoir of genetic and biological diversity continues to yield exciting discoveries.

2,438 citations


Journal ArticleDOI
TL;DR: The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.
Abstract: Several well-recognized puzzles in microbiology have remained unsolved for decades. These include latent bacterial infections, unculturable microorganisms, persister cells and biofilm multidrug tolerance. Accumulating evidence suggests that these seemingly disparate phenomena result from the ability of bacteria to enter into a dormant (non-dividing) state. The molecular mechanisms that underlie the formation of dormant persister cells are now being unravelled and are the focus of this Review.

1,823 citations


Journal ArticleDOI
TL;DR: An overview of the current knowledge of the genus Acinetobacter is presented, with the emphasis on the clinically most important species, Acetobacter baumannii.
Abstract: Since the 1970s, the spread of multidrug-resistant (MDR) Acinetobacter strains among critically ill, hospitalized patients, and subsequent epidemics, have become an increasing cause of concern. Reports of community-acquired Acinetobacter infections have also increased over the past decade. A recent manifestation of MDR Acinetobacter that has attracted public attention is its association with infections in severely injured soldiers. Here, we present an overview of the current knowledge of the genus Acinetobacter, with the emphasis on the clinically most important species, Acinetobacter baumannii.

1,558 citations


Journal ArticleDOI
TL;DR: Millefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphoteric in B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies.
Abstract: Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients.

1,463 citations


Journal ArticleDOI
TL;DR: The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps.
Abstract: Hepatitis C virus (HCV) afflicts more than 170 million people worldwide causing chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The recent development of complete cell-culture systems for HCV has accelerated the pace of hepatitis research. Specifically, these techniques have provided new insights into the virus lifecycle that are reviewed here. This should pave the way for developing bespoke and effective antiviral therapies and vaccines. Exciting progress has recently been made in understanding the replication of hepatitis C virus, a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma worldwide. The development of complete cell-culture systems should now enable the systematic dissection of the entire viral lifecycle, providing insights into the hitherto difficult-to-study early and late steps. These efforts have already translated into the identification of novel antiviral targets and the development of new therapeutic strategies, some of which are currently undergoing clinical evaluation.

1,286 citations


Journal ArticleDOI
TL;DR: Generalization of the coral probiotic hypothesis has led to the hologenome theory of evolution, which proposes the occurrence of a dynamic relationship between symbiotic microorganisms and corals that selects for the coral holobiont that is best suited for the prevailing environmental conditions.
Abstract: Coral microbiology is an emerging field, driven largely by a desire to understand, and ultimately prevent, the worldwide destruction of coral reefs. The mucus layer, skeleton and tissues of healthy corals all contain large populations of eukaryotic algae, bacteria and archaea. These microorganisms confer benefits to their host by various mechanisms, including photosynthesis, nitrogen fixation, the provision of nutrients and infection prevention. Conversely, in conditions of environmental stress, certain microorganisms cause coral bleaching and other diseases. Recent research indicates that corals can develop resistance to specific pathogens and adapt to higher environmental temperatures. To explain these findings the coral probiotic hypothesis proposes the occurrence of a dynamic relationship between symbiotic microorganisms and corals that selects for the coral holobiont that is best suited for the prevailing environmental conditions. Generalization of the coral probiotic hypothesis has led us to propose the hologenome theory of evolution.

1,261 citations


Journal ArticleDOI
TL;DR: The need to examine the biochemical interactions of microorganisms with ocean systems at the nanometre to millimetre scale is stressed — a scale that is relevant to microbial activities and must be scaled up to make useful predictions of how marine ecosystems in the whole ocean might respond to global change.
Abstract: Despite the impressive advances that have been made in assessing the diversity of marine microorganisms, the mechanisms that underlie the participation of microorganisms in marine food webs and biogeochemical cycles are poorly understood. Here, we stress the need to examine the biochemical interactions of microorganisms with ocean systems at the nanometre to millimetre scale--a scale that is relevant to microbial activities. The local impact of microorganisms on biogeochemical cycles must then be scaled up to make useful predictions of how marine ecosystems in the whole ocean might respond to global change. This approach to microbial oceanography is not only helpful, but is in fact indispensable.

1,247 citations


Journal ArticleDOI
TL;DR: Understanding the molecular diversity that underlies resistance will inform the use of these drugs and guide efforts to develop new efficacious antibiotics.
Abstract: Resistance to antibiotics in microorganisms predates the use of these drugs. This Review examines why antibiotic resistance is inevitable and where it originates from.

1,166 citations


Journal ArticleDOI
TL;DR: It is argued that the full potential of the ongoing revolution in microbial ecology will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.
Abstract: Microbial ecology is currently undergoing a revolution, with repercussions spreading throughout microbiology, ecology and ecosystem science. The rapid accumulation of molecular data is uncovering vast diversity, abundant uncultivated microbial groups and novel microbial functions. This accumulation of data requires the application of theory to provide organization, structure, mechanistic insight and, ultimately, predictive power that is of practical value, but the application of theory in microbial ecology is currently very limited. Here we argue that the full potential of the ongoing revolution will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.

874 citations


Journal ArticleDOI
TL;DR: An overview of the structure, function and generation of NETs, and their role in infections is given.
Abstract: Neutrophils are one of the main types of effector cell in the innate immune system and were first shown to effectively kill microorganisms by phagocytosis more than 100 years ago. Recently, however, it has been found that stimulated neutrophils can also produce extracellular structures called neutrophil extracellular traps (NETs) that capture and kill microorganisms. This Progress article gives an overview of the structure, function and generation of NETs, and their role in infections.

854 citations


Journal ArticleDOI
TL;DR: Recent discoveries about the mutual recognition process that allows the model rhizobial symbiont Sinorhizobium meliloti to invade and differentiate inside its host plant alfalfa and the model host plant barrel medic are reviewed.
Abstract: Nitrogen-fixing rhizobial bacteria and leguminous plants have evolved complex signal exchange mechanisms that allow a specific bacterial species to induce its host plant to form invasion structures through which the bacteria can enter the plant root. Once the bacteria have been endocytosed within a host-membrane-bound compartment by root cells, the bacteria differentiate into a new form that can convert atmospheric nitrogen into ammonia. Bacterial differentiation and nitrogen fixation are dependent on the microaerobic environment and other support factors provided by the plant. In return, the plant receives nitrogen from the bacteria, which allows it to grow in the absence of an external nitrogen source. Here, we review recent discoveries about the mutual recognition process that allows the model rhizobial symbiont Sinorhizobium meliloti to invade and differentiate inside its host plant alfalfa (Medicago sativa) and the model host plant barrel medic (Medicago truncatula).

Journal ArticleDOI
TL;DR: This Review summarizes methods for constructing systems and structures at micron or submicron scales that have applications in microbiology and focuses on the application of soft lithographic techniques to the study of microorganisms.
Abstract: This Review summarizes methods for constructing systems and structures at micron or submicron scales that have applications in microbiology. These tools make it possible to manipulate individual cells and their immediate extracellular environments and have the capability to transform the study of microbial physiology and behaviour. Because of their simplicity, low cost and use in microfabrication, we focus on the application of soft lithographic techniques to the study of microorganisms, and describe several key areas in microbiology in which the development of new microfabricated materials and tools can have a crucial role.

Journal ArticleDOI
TL;DR: C. jejuni establishes persistent, benign infections in chickens and is rapidly cleared by many strains of laboratory mouse, but causes significant inflammation and enteritis in humans.
Abstract: Campylobacter jejuni is a foodborne bacterial pathogen that is common in the developed world. However, we know less about its biology and pathogenicity than we do about other less prevalent pathogens. Interest in C. jejuni has increased in recent years as a result of the growing appreciation of its importance as a pathogen and the availability of new model systems and genetic and genomic technologies. C. jejuni establishes persistent, benign infections in chickens and is rapidly cleared by many strains of laboratory mouse, but causes significant inflammation and enteritis in humans. Comparing the different host responses to C. jejuni colonization should increase our understanding of this organism.

Journal ArticleDOI
TL;DR: Given the unique composition of this secretion system, and its general importance, it is proposed that, in line with the accepted nomenclature, it should be called type VII secretion.
Abstract: Recent evidence shows that mycobacteria have developed novel and specialized secretion systems for the transport of extracellular proteins across their hydrophobic, and highly impermeable, cell wall. Strikingly, mycobacterial genomes encode up to five of these transport systems. Two of these systems, ESX-1 and ESX-5, are involved in virulence - they both affect the cell-to-cell migration of pathogenic mycobacteria. Here, we discuss this novel secretion pathway and consider variants that are present in various Gram-positive bacteria. Given the unique composition of this secretion system, and its general importance, we propose that, in line with the accepted nomenclature, it should be called type VII secretion.

Journal ArticleDOI
TL;DR: The hypothesis that chronic energy stress is the primary selective pressure governing the evolution of the Archaea is proposed and proposed, and biochemical mechanisms that enable archaea to cope with chronicEnergy stress include low-permeability membranes and specific catabolic pathways.
Abstract: The three domains of life on Earth include the two prokaryotic groups, Archaea and Bacteria. The Archaea are distinguished from Bacteriabased on phylogenetic and biochemical differences, but currently there is no unifying ecological principle to differentiate these groups. The ecology of the Archaea is reviewed here in terms of cellular bioenergetics. Adaptation to chronic energy stress is hypothesized to be the crucial factor that distinguishes the Archaea from Bacteria. The biochemical mechanisms that enable archaea to cope with chronic energy stress include low-permeability membranes and specific catabolic pathways. Based on the ecological unity and biochemical adaptations among archaea, I propose the hypothesis that chronic energy stress is the primary selective pressure governing the evolution of the Archaea.

Journal ArticleDOI
TL;DR: This Review explores how Mycobacterium tuberculosis influences granuloma formation and maintenance, and ensures the spread of the disease.
Abstract: Tuberculosis (TB), an illness that mainly affects the respiratory system, is one of the world's most pernicious diseases. TB currently infects one-third of the world's population and kills approximately 1.7 million people each year. Most infected individuals fail to progress to full-blown disease because the TB bacilli are 'walled off' by the immune system inside a tissue nodule known as a granuloma. The granuloma's primary function is one of containment and it prevents the dissemination of the mycobacteria. But what is the role of the TB bacillus in the progression of the granuloma? This Review explores how Mycobacterium tuberculosis influences granuloma formation and maintenance, and ensures the spread of the disease.

Journal ArticleDOI
Bruno Guy1
TL;DR: The research that has made it possible for vaccinologists to now be able to choose between a large panel of adjuvants, which potentially can act synergistically, and combine them in formulations that are specifically adapted to each target and to the relevant correlate(s) of protection is discussed.
Abstract: Developing efficient and safe adjuvants for use in human vaccines remains both a challenge and a necessity. Past approaches have been largely empirical and generally used a single type of adjuvant, such as aluminium salts or emulsions. However, new vaccine targets often require the induction of well-defined cell-mediated responses in addition to antibodies, and thus new immunostimulants are required. Recent advances in basic immunology have elucidated how early innate immune signals can shape subsequent adaptive responses and this, coupled with improvements in biochemical techniques, has led to the design and development of more specific and focused adjuvants. In this Review, I discuss the research that has made it possible for vaccinologists to now be able to choose between a large panel of adjuvants, which potentially can act synergistically, and combine them in formulations that are specifically adapted to each target and to the relevant correlate(s) of protection.

Journal ArticleDOI
TL;DR: The unique immunological concerns in dengue virus vaccine development are discussed and the current prospects for the development of an acceptable vaccine are discussed, with a goal that is likely to be reached in the near future.
Abstract: The number of cases of severe dengue disease continues to grow in endemic areas of southeast Asia, Central and South America, and other subtropical regions. Children bear the greatest burden of disease, and the development of an effective vaccine remains a global public health priority. A tetravalent vaccine is urgently needed and must be effective against all four dengue virus serotypes, be cost-effective and provide long-term protection. In this Review we discuss the unique immunological concerns in dengue virus vaccine development and the current prospects for the development of an acceptable vaccine, a goal that is likely to be reached in the near future.

Journal ArticleDOI
TL;DR: Microbial biodiversity and function in these intriguing environments, where energy is most depleted, might even be based on the cleavage of water by natural radioisotopes, are reviewed.
Abstract: The seabed is a diverse environment that ranges from the desert-like deep seafloor to the rich oases that are present at seeps, vents, and food falls such as whales, wood or kelp. As well as the sedimentation of organic material from above, geological processes transport chemical energy — hydrogen, methane, hydrogen sulphide and iron — to the seafloor from the subsurface below, which provides a significant proportion of the deep-sea energy. At the sites on the seafloor where chemical energy is delivered, rich and diverse microbial communities thrive. However, most subsurface microorganisms live in conditions of extreme energy limitation, with mean generation times of up to thousands of years. Even in the most remote subsurface habitats, temperature rather than energy seems to set the ultimate limit for life, and in the deep biosphere, where energy is most depleted, life might even be based on the cleavage of water by natural radioisotopes. Here, we review microbial biodiversity and function in these intriguing environments.

Journal ArticleDOI
TL;DR: A multifactorial model by which biofilm populations can withstand metal toxicity by a process of cellular diversification is proposed.
Abstract: Geochemical cycling and industrial pollution have made toxic metal ions a pervasive environmental pressure throughout the world. Biofilm formation is a strategy that microorganisms might use to survive a toxic flux in these inorganic compounds. Evidence in the literature suggests that biofilm populations are protected from toxic metals by the combined action of chemical, physical and physiological phenomena that are, in some instances, linked to phenotypic variation among the constituent biofilm cells. Here, we propose a multifactorial model by which biofilm populations can withstand metal toxicity by a process of cellular diversification.

Journal ArticleDOI
TL;DR: It is argued that these conflicting concepts can be unified by a new hypothesis, efficiency sensing, and that some of the problems associated with signalling in complex environments, as well as the problem of maintaining honesty in signalling, can be avoided when the signalling cells grow in microcolonies.
Abstract: Quorum sensing faces evolutionary problems from non-producing or over-producing cheaters Such problems are circumvented in diffusion sensing, an alternative explanation for quorum sensing However, both explanations face the problems of signalling in complex environments such as the rhizosphere where, for example, the spatial distribution of cells can be more important for sensing than cell density, which we show by mathematical modelling We argue that these conflicting concepts can be unified by a new hypothesis, efficiency sensing, and that some of the problems associated with signalling in complex environments, as well as the problem of maintaining honesty in signalling, can be avoided when the signalling cells grow in microcolonies

Journal ArticleDOI
TL;DR: Natural killer T (NKT) cells combine features of the innate and adaptive immune systems and respond to innate cytokines produced by dendritic cells that have been activated by microbes.
Abstract: Natural killer T (NKT) cells influence diverse immune responses, combining features of both the innate and adaptive immune systems. This Review examines the unique role of invariant NKT cells (which have an invariant T-cell-receptor α-chain) in the response to various microbial pathogens. Natural killer T (NKT) cells combine features of the innate and adaptive immune systems. Recently, it has become evident that these T cells have crucial roles in the response to infectious agents. The antigen receptor expressed by NKT cells directly recognizes unusual glycolipids that are part of the membrane of certain Gram-negative bacteria and spirochetes. Moreover, even in the absence of microbial glycolipid antigens, these T cells respond to innate cytokines produced by dendritic cells that have been activated by microbes. This indirect sensing of infection, by responding to cytokines from activated dendritic cells, allows NKT cells to react to a broad range of infectious agents.

Journal ArticleDOI
TL;DR: Insect and mammalian PGRPs defend host cells against infection through very different mechanisms, and these contrasting modes of action are reviewed.
Abstract: Peptidoglycan recognition proteins (PGRPs) are innate immune receptors that are highly conserved from insects to mammals. Recent studies have revealed that, despite this conservation, insect and mammalian PGRPs defend host cells against infection by different mechanisms. Julien Royet and Roman Dziarski review these contrasting modes of action.

Journal ArticleDOI
TL;DR: Single-virus tracking in living cells allows us to follow the fate of individual virus particles and monitor dynamic interactions between viruses and cellular structures, revealing previously unobservable infection steps.
Abstract: This Review describes how single-virus tracking can be used to monitor the journey that viruses make through cells in exquisite detail. With specific examples of the entry, cellular transport and exit of selected viruses, the technicalities and benefits of this approach are revealed.

Journal ArticleDOI
TL;DR: This Review presents an overview of both the mechanism and regulation of bacterial DNA replication initiation, with emphasis on the features that are similar in eukaryotic and archaeal systems.
Abstract: In all organisms, multi-subunit replicases are responsible for the accurate duplication of genetic material during cellular division. Initiator proteins control the onset of DNA replication and direct the assembly of replisomal components through a series of precisely timed protein-DNA and protein-protein interactions. Recent structural studies of the bacterial protein DnaA have helped to clarify the molecular mechanisms underlying initiator function, and suggest that key structural features of cellular initiators are universally conserved. Moreover, it appears that bacteria use a diverse range of regulatory strategies dedicated to tightly controlling replication initiation; in many cases, these mechanisms are intricately connected to the activities of DnaA at the origin of replication. This Review presents an overview of both the mechanism and regulation of bacterial DNA replication initiation, with emphasis on the features that are similar in eukaryotic and archaeal systems.

Journal ArticleDOI
TL;DR: The remarkable ability of bacteria to adapt efficiently to a wide range of nutritional environments reflects their use of overlapping regulatory systems that link gene expression to intracellular pools of a small number of key metabolites.
Abstract: Almost all bacteria can adapt efficiently to different nutritional environments by using global regulators that link gene expression to the available intracellular pools of a small number of key metabolites. Here, Abraham L. Sonenshein reviews how Bacillus subtilis uses global regulators to manage traffic through two metabolic intersections that determine the flow of carbon and nitrogen to and from crucial metabolites.

Journal ArticleDOI
TL;DR: It is argued that H. pylori uses mutation and recombination processes to adapt to its individual host by modifying molecules that interact with the host, and put forward the hypothesis that the lack of opportunity for intraspecies recombination as a result of the decreasing prevalence of H.pylori could accelerate its disappearance from Western populations.
Abstract: Helicobacter pylori colonizes the stomachs of more than 50% of the world's population, making it one of the most successful of all human pathogens. One striking characteristic of H. pylori biology is its remarkable allelic diversity and genetic variability. Not only does almost every infected person harbour their own individual H. pylori strain, but strains can undergo genetic alteration in vivo, driven by an elevated mutation rate and frequent intraspecific recombination. This genetic variability, which affects both housekeeping and virulence genes, has long been thought to contribute to host adaptation, and several recently published studies support this concept. We review the available knowledge relating to the genetic variation of H. pylori, with special emphasis on the changes that occur during chronic colonization, and argue that H. pylori uses mutation and recombination processes to adapt to its individual host by modifying molecules that interact with the host. Finally, we put forward the hypothesis that the lack of opportunity for intraspecies recombination as a result of the decreasing prevalence of H. pylori could accelerate its disappearance from Western populations.

Journal ArticleDOI
TL;DR: Recent progress is reviewed in understanding of how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental cues.
Abstract: All living organisms use numerous signal-transduction systems to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we review recent progress in our understanding of how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental cues.

Journal ArticleDOI
TL;DR: A functional comparison between bacterial programmed cell death and apoptosis is provided and the hypothesis that the differential regulation of these processes during biofilm development contributes to the antibiotic tolerance of biofilm cells is explored.
Abstract: Recent studies have revealed that the regulated death of bacterial cells is important for biofilm development. Following cell death, a sub-population of the dead bacteria lyse and release genomic DNA, which then has an essential role in intercellular adhesion and biofilm stability. This Opinion focuses on the role of regulated cell death and lysis in biofilm development and provides a functional comparison between bacterial programmed cell death and apoptosis. The hypothesis that the differential regulation of these processes during biofilm development contributes to the antibiotic tolerance of biofilm cells is also explored.

Journal ArticleDOI
TL;DR: It is suggested that climate determines the equator- to-pole and continent-to-land thermal gradients that provide energy for the wind-driven turbulent mixing in the upper ocean, which controls the nutrient fluxes that determine cell size and taxa-level distributions.
Abstract: Climate strongly influences the distribution and diversity of animals and plants, but its affect on microbial communities is poorly understood. By using resource competition theory, fundamental physical principles and the fossil record we review how climate selects marine eukaryotic phytoplankton taxa. We suggest that climate determines the equator-to-pole and continent-to-land thermal gradients that provide energy for the wind-driven turbulent mixing in the upper ocean. This mixing, in turn, controls the nutrient fluxes that determine cell size and taxa-level distributions. Understanding this chain of linked processes will allow informed predictions to be made about how phytoplankton communities will change in the future.