With the number of published microbial genomes now in excess of 100, any new genome that is sequenced is likely to have a close relative available for comparison. Indeed, it is increasingly difficult to perform any genomic analysis that is not comparative. This should, however, not be seen as a drawback; it is often the case that a large amount of information can be drawn from these comparisons, especially between closely related organisms. Several genome sequences published recently indicate the value of comparisons at the genomic level.
Numerous studies indicate that carbon monoxide (CO) participates in a broader range of processes than any other single molecule, ranging from subcellular to planetary scales. Despite its toxicity to many organisms, a diverse group of bacteria that span multiple phylogenetic lineages metabolize CO. These bacteria are globally distributed and include pathogens, plant symbionts and biogeochemically important lineages in soils and the oceans. New molecular and isolation techniques, as well as genome sequencing, have greatly expanded our knowledge of the diversity of CO oxidizers. Here, we present a newly emerging picture of the distribution, diversity and ecology of aerobic CO-oxidizing bacteria.
Eukaryotic cells can initiate several distinct programmes of self-destruction, and the nature of the cell death process (non-inflammatory or proinflammatory) instructs responses of neighbouring cells, which in turn dictates important systemic physiological outcomes. Pyroptosis, or caspase 1-dependent cell death, is inherently inflammatory, is triggered by various pathological stimuli, such as stroke, heart attack or cancer, and is crucial for controlling microbial infections. Pathogens have evolved mechanisms to inhibit pyroptosis, enhancing their ability to persist and cause disease. Ultimately, there is a competition between host and pathogen to regulate pyroptosis, and the outcome dictates life or death of the host.
Submarine hydrothermal vents are geochemically reactive habitats that harbour rich microbial communities. There are striking parallels between the chemistry of the H(2)-CO(2) redox couple that is present in hydrothermal systems and the core energy metabolic reactions of some modern prokaryotic autotrophs. The biochemistry of these autotrophs might, in turn, harbour clues about the kinds of reactions that initiated the chemistry of life. Hydrothermal vents thus unite microbiology and geology to breathe new life into research into one of biology's most important questions - what is the origin of life?
The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.
Fungi produce a multitude of low-molecular-mass compounds known as secondary metabolites, which have roles in a range of cellular processes such as transcription, development and intercellular communication. In addition, many of these compounds now have important applications, for instance, as antibiotics or immunosuppressants. Genome mining efforts indicate that the capability of fungi to produce secondary metabolites has been substantially underestimated because many of the fungal secondary metabolite biosynthesis gene clusters are silent under standard cultivation conditions. In this Review, I describe our current understanding of the regulatory elements that modulate the transcription of genes involved in secondary metabolism. I also discuss how an improved knowledge of these regulatory elements will ultimately lead to a better understanding of the physiological and ecological functions of these important compounds and will pave the way for a novel avenue to drug discovery through targeted activation of silent gene clusters.
Microorganisms and their hosts communicate with each other through an array of hormonal signals. This cross-kingdom cell-to-cell signalling involves small molecules, such as hormones that are produced by eukaryotes and hormone-like chemicals that are produced by bacteria. Cell-to-cell signalling between bacteria, usually referred to as quorum sensing, was initially described as a means by which bacteria achieve signalling in microbial communities to coordinate gene expression within a population. Recent evidence shows, however, that quorum-sensing signalling is not restricted to bacterial cell-to-cell communication, but also allows communication between microorganisms and their hosts.
The nucleolus is a dynamic subnuclear structure with roles in ribosome subunit biogenesis, mediation of cell-stress responses and regulation of cell growth. The proteome and structure of the nucleolus are constantly changing in response to metabolic conditions. RNA viruses interact with the nucleolus to usurp host-cell functions and recruit nucleolar proteins to facilitate virus replication. Investigating the interactions between RNA viruses and the nucleolus will facilitate the design of novel anti-viral therapies, such as recombinant vaccines and therapeutic molecular interventions, and also contribute to a more detailed understanding of the cell biology of the nucleolus.
The arid soils of the Antarctic Dry Valleys constitute some of the oldest, coldest, driest and most oligotrophic soils on Earth. Early studies suggested that the Dry Valley soils contained, at best, very low levels of viable microbiota. However, recent applications of molecular methods have revealed a dramatically contrasting picture - a very wide diversity of microbial taxa, many of which are uncultured and taxonomically unique, and a community that seems to be structured solely by abiotic processes. Here we review our understanding of these extreme Antarctic terrestrial microbial communities, with particular emphasis on the factors that are involved in their development, distribution and maintenance in these cold desert environments.
The pathogenesis of Legionella pneumophila is derived from its growth within lung macrophages after aerosols are inhaled from contaminated water sources. Interest in this bacterium stems from its ability to manipulate host cell vesicular-trafficking pathways and establish a membrane-bound replication vacuole, making it a model for intravacuolar pathogens. Establishment of the replication compartment requires a specialized translocation system that transports a large cadre of protein substrates across the vacuolar membrane. These substrates regulate vesicle traffic and survival pathways in the host cell. This Review focuses on the strategies that L. pneumophila uses to establish intracellular growth and evaluates why this microorganism has accumulated an unprecedented number of translocated substrates that are targeted at host cells.
Bacteria use type IV secretion systems for two fundamental objectives related to pathogenesis--genetic exchange and the delivery of effector molecules to eukaryotic target cells. Whereas gene acquisition is an important adaptive mechanism that enables pathogens to cope with a changing environment during invasion of the host, interactions between effector and host molecules can suppress defence mechanisms, facilitate intracellular growth and even induce the synthesis of nutrients that are beneficial to bacterial colonization. Rapid progress has been made towards defining the structures and functions of type IV secretion machines, identifying the effector molecules, and elucidating the mechanisms by which the translocated effectors subvert eukaryotic cellular processes during infection.
A fundamental principle of exponential bacterial growth is that no more ribosomes are produced than are necessary to support the balance between nutrient availability and protein synthesis. Although this conclusion was first expressed more than 40 years ago, a full understanding of the molecular mechanisms involved remains elusive and the issue is still controversial. There is currently agreement that, although many different systems are undoubtedly involved in fine-tuning this balance, an important control, and in our opinion perhaps the main control, is regulation of the rate of transcription initiation of the stable (ribosomal and transfer) RNA transcriptons. In this review, we argue that regulation of DNA supercoiling provides a coherent explanation for the main modes of transcriptional control - stringent control, growth-rate control and growth-phase control - during the normal growth of Escherichia coli.
Following a sixty-year hiatus in western medicine, bacteriophages (phages) are again being advocated for treating and preventing bacterial infections. Are attempts to use phages for clinical and environmental applications more likely to succeed now than in the past? Will phage therapy and prophylaxis suffer the same fates as antibiotics--treatment failure due to acquired resistance and ever-increasing frequencies of resistant pathogens? Here, the population and evolutionary dynamics of bacterial-phage interactions that are relevant to phage therapy and prophylaxis are reviewed and illustrated with computer simulations.
The emergence and increasing prevalence of bacterial strains that are resistant to available antibiotics demand the discovery of new therapeutic approaches. Targeting bacterial virulence is an alternative approach to antimicrobial therapy that offers promising opportunities to inhibit pathogenesis and its consequences without placing immediate life-or-death pressure on the target bacterium. Certain virulence factors have been shown to be potential targets for drug design and therapeutic intervention, whereas new insights are crucial for exploiting others. Targeting virulence represents a new paradigm to empower the clinician to prevent and treat infectious diseases.
Hundreds of millions of litres of petroleum enter the environment from both natural and anthropogenic sources every year. The input from natural marine oil seeps alone would be enough to cover all of the world's oceans in a layer of oil 20 molecules thick. That the globe is not swamped with oil is testament to the efficiency and versatility of the networks of microorganisms that degrade hydrocarbons, some of which have recently begun to reveal the secrets of when and how they exploit hydrocarbons as a source of carbon and energy.
Fungi possess the biochemical and ecological capacity to degrade environmental organic chemicals and to decrease the risk associated with metals, metalloids and radionuclides, either by chemical modification or by influencing chemical bioavailability. Furthermore, the ability of these fungi to form extended mycelial networks, the low specificity of their catabolic enzymes and their independence from using pollutants as a growth substrate make these fungi well suited for bioremediation processes. However, despite dominating the living biomass in soil and being abundant in aqueous systems, fungi have not been exploited for the bioremediation of such environments. In this Review, we describe the metabolic and ecological features that make fungi suited for use in bioremediation and waste treatment processes, and discuss their potential for applications on the basis of these strengths.
Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.
We know very little about the metabolic functioning and evolutionary dynamics of microbial communities. Recent advances in comprehensive, sequencing-based methods, however, are laying a molecular foundation for new insights into how microbial communities shape the Earth's biosphere. Here we explore the convergence of microbial ecology, genomics, biological mass spectrometry and informatics that form the new field of microbial community proteogenomics. We discuss the first applications of proteogenomics and its potential for studying the physiology, ecology and evolution of microbial populations and communities.
We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in the regulation of chromosome structure and segregation may in fact function primarily in supporting such an entropy-driven segregation mechanism by regulating the physical state of chromosomes. We conclude that bacterial chromosome segregation is best understood in terms of spontaneous demixing of daughter strands. Our concept may also have important implications for chromosome segregation in eukaryotes, in which spindle-dependent chromosome movement follows an extended period of sister chromatid demixing and compaction.
The availability of the first molecular clone of the hepatitis C virus (HCV) genome allowed the identification and biochemical characterization of two viral enzymes that are targets for antiviral therapy: the protease NS3-4A and the RNA-dependent RNA polymerase NS5B. With the advent of cell culture systems that can recapitulate either the intracellular steps of the viral replication cycle or the complete cycle, additional drug targets have been identified, most notably the phosphoprotein NS5A, but also host cell factors that promote viral replication, such as cyclophilin A. Here, we review insights into the structures of these proteins and the mechanisms by which they contribute to the HCV replication cycle, and discuss how these insights have facilitated the development of new, directly acting antiviral compounds that have started to enter the clinic.
Herpes simplex viruses (HSV) can undergo a lytic infection in epithelial cells and a latent infection in sensory neurons. During latency the virus persists until reactivation, which leads to recurrent productive infection and transmission to a new host. How does HSV undergo such different types of infection in different cell types? Recent research indicates that regulation of the assembly of chromatin on HSV DNA underlies the lytic versus latent decision of HSV. We propose a model for the decision to undergo a lytic or a latent infection in which HSV encodes gene products that modulate chromatin structure towards either euchromatin or heterochromatin, and we discuss the implications of this model for the development of therapeutics for HSV infections.
Whereas most prokaryotes rely on binary fission for propagation, many species use alternative mechanisms, which include multiple offspring formation and budding, to reproduce. In some bacterial species, these eccentric reproductive strategies are essential for propagation, whereas in others the programmes are used conditionally. Although there are tantalizing images and morphological descriptions of these atypical developmental processes, none of these reproductive structures are characterized at the molecular genetic level. Now, with newly available analytical techniques, model systems to study these alternative reproductive programmes are being developed.