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Annual Review of Microbiology - Volume 76, 2022
Volume 76, 2022
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My Personal Journey from the Fascination for Phages to a Tumor-Inducing Fungal Pathogen of Corn
Vol. 76 (2022), pp. 1–19More LessMy path in science began with a fascination for microbiology and phages and later involved a switch of subjects to the fungus Ustilago maydis and how it causes disease in maize. I will not provide a review of my work but rather focus on decisive findings, serendipitous, lucky moments when major advances made the U. maydis–maize system what it is now—a well-established model for biotrophic fungi. I also want to share with you the joy of finding the needle in a haystack at the very end of my scientific career, a fungal structure likely used for effector delivery, and how we were able to translate this into a potential application in agriculture.
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Toxin-Antitoxin Systems as Phage Defense Elements
Vol. 76 (2022), pp. 21–43More LessToxin-antitoxin (TA) systems are ubiquitous genetic elements in bacteria that consist of a growth-inhibiting toxin and its cognate antitoxin. These systems are prevalent in bacterial chromosomes, plasmids, and phage genomes, but individual systems are not highly conserved, even among closely related strains. The biological functions of TA systems have been controversial and enigmatic, although a handful of these systems have been shown to defend bacteria against their viral predators, bacteriophages. Additionally, their patterns of conservation—ubiquitous, but rapidly acquired and lost from genomes—as well as the co-occurrence of some TA systems with known phage defense elements are suggestive of a broader role in mediating phage defense. Here, we review the existing evidence for phage defense mediated by TA systems, highlighting how toxins are activated by phage infection and how toxins disrupt phage replication. We also discuss phage-encoded systems that counteract TA systems, underscoring the ongoing coevolutionary battle between bacteria and phage. We anticipate that TA systems will continue to emerge as central players in the innate immunity of bacteria against phage.
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The Versatile Roles of Type III Secretion Systems in Rhizobium-Legume Symbioses
Vol. 76 (2022), pp. 45–65More LessTo suppress plant immunity and promote the intracellular infection required for fixing nitrogen for the benefit of their legume hosts, many rhizobia use type III secretion systems (T3SSs) that deliver effector proteins (T3Es) inside host cells. As reported for interactions between pathogens and host plants, the immune system of legume hosts and the cocktail of T3Es secreted by rhizobia determine the symbiotic outcome. If they remain undetected, T3Es may reduce plant immunity and thus promote infection of legumes by rhizobia. If one or more of the secreted T3Es are recognized by the cognate plant receptors, defense responses are triggered and rhizobial infection may abort. However, some rhizobial T3Es can also circumvent the need for nodulation (Nod) factors to trigger nodule formation. Here we review the multifaceted roles played by rhizobial T3Es during symbiotic interactions with legumes.
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Plasmodium Egress Across the Parasite Life Cycle
Vol. 76 (2022), pp. 67–90More LessHuman malaria, caused by infection with Plasmodium parasites, remains one of the most important global public health problems, with the World Health Organization reporting more than 240 million cases and 600,000 deaths annually as of 2020 (World malaria report 2021). Our understanding of the biology of these parasites is critical for development of effective therapeutics and prophylactics, including both antimalarials and vaccines. Plasmodium is a protozoan organism that is intracellular for most of its life cycle. However, to complete its complex life cycle and to allow for both amplification and transmission, the parasite must egress out of the host cell in a highly regulated manner. This review discusses the major pathways and proteins involved in the egress events during the Plasmodium life cycle—merozoite and gametocyte egress out of red blood cells, sporozoite egress out of the oocyst, and merozoite egress out of the hepatocyte. The similarities, as well as the differences, between the various egress pathways of the parasite highlight both novel cell biology and potential therapeutic targets to arrest its life cycle.
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Metabolic Reprogramming and Longevity in Quiescence
Vol. 76 (2022), pp. 91–111More LessSince Jacques Monod's foundational work in the 1940s, investigators studying bacterial physiology have largely (but not exclusively) focused on the exponential phase of bacterial cultures, which is characterized by rapid growth and high biosynthesis activity in the presence of excess nutrients. However, this is not the predominant state of bacterial life. In nature, most bacteria experience nutrient limitation most of the time. In fact, investigators even prior to Monod had identified other aspects of bacterial growth, including what is now known as the stationary phase, when nutrients become limiting. This review will discuss how bacteria transition to growth arrest in response to nutrient limitation through changes in transcription, translation, and metabolism. We will then examine how these changes facilitate survival during potentially extended periods of nutrient limitation, with particular attention to the metabolic strategies that underpin bacterial longevity in this state.
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Division and Transmission: Malaria Parasite Development in the Mosquito
Vol. 76 (2022), pp. 113–134More LessThe malaria parasite life cycle alternates between two hosts: a vertebrate and the female Anopheles mosquito vector. Cell division, proliferation, and invasion are essential for parasite development, transmission, and survival. Most research has focused on Plasmodium development in the vertebrate, which causes disease; however, knowledge of malaria parasite development in the mosquito (the sexual and transmission stages) is now rapidly accumulating, gathered largely through investigation of the rodent malaria model, with Plasmodium berghei. In this review, we discuss the seminal genome-wide screens that have uncovered key regulators of cell proliferation, invasion, and transmission during Plasmodium sexual development. Our focus is on the roles of transcription factors, reversible protein phosphorylation, and molecular motors. We also emphasize the still-unanswered important questions around key pathways in cell division during the vector transmission stages and how they may be targeted in future studies.
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Epigenetic Reprogramming in Host-Parasite Coevolution: The Toxoplasma Paradigm
Vol. 76 (2022), pp. 135–155More LessLike many intracellular pathogens, the protozoan parasite Toxoplasma gondii has evolved sophisticated mechanisms to promote its transmission and persistence in a variety of hosts by injecting effector proteins that manipulate many processes in the cells it invades. Specifically, the parasite diverts host epigenetic modulators and modifiers from their native functions to rewire host gene expression to counteract the innate immune response and to limit its strength. The arms race between the parasite and its hosts has led to accelerated adaptive evolution of effector proteins and the unconventional secretion routes they use. This review provides an up-to-date overview of how T. gondii effectors, through the evolution of intrinsically disordered domains, the formation of supramolecular complexes, and the use of molecular mimicry, target host transcription factors that act as coordinating nodes, as well as chromatin-modifying enzymes, to control the fate of infected cells and ultimately the outcome of infection.
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Sirtuins in Epigenetic Silencing and Control of Gene Expression in Model and Pathogenic Fungi
Vol. 76 (2022), pp. 157–178More LessFungi, including yeasts, molds, and mushrooms, proliferate on decaying matter and then adopt quiescent forms once nutrients are depleted. This review explores how fungi use sirtuin deacetylases to sense and respond appropriately to changing nutrients. Because sirtuins are NAD+-dependent deacetylases, their activity is sensitive to intracellular NAD+ availability. This allows them to transmit information about a cell's metabolic state on to the biological processes they influence. Fungal sirtuins are primarily known to deacetylate histones, repressing transcription and modulating genome stability. Their target genes include those involved in NAD+ homeostasis, metabolism, sporulation, secondary metabolite production, and virulence traits of pathogenic fungi. By targeting different genes over evolutionary time, sirtuins serve as rewiring points that allow organisms to evolve novel responses to low NAD+ stress by bringing relevant biological processes under the control of sirtuins.
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Microbial Interspecies Interactions and Their Impact on the Emergence and Spread of Antimicrobial Resistance
Vol. 76 (2022), pp. 179–192More LessBacteria are social organisms that commonly live in dense communities surrounded by a multitude of other species. The competitive and cooperative interactions between these species not only shape the bacterial communities but also influence their susceptibility to antimicrobials. While several studies have shown that mixed-species communities are more tolerant toward antimicrobials than their monospecies counterparts, only limited empirical data are currently available on how interspecies interactions influence resistance development. We here propose a theoretic framework outlining the potential impact of interspecies social behavior on different aspects of resistance development. We identify factors by which interspecies interactions might influence resistance evolution and distinguish between their effect on (a) the emergence of a resistant mutant and (b) the spread of this resistance throughout the population. Our analysis indicates that considering the social life of bacteria is imperative to the rational design of more effective antibiotic treatment strategies with a minimal hazard for resistance development.
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Interdependency and Redundancy Add Complexity and Resilience to Biogenesis of Bacterial Ribosomes
Vol. 76 (2022), pp. 193–210More LessThe pace and efficiency of ribosomal subunit production directly impact the fitness of bacteria. Biogenesis demands more than just the union of ribosomal components, including RNA and proteins, to form this functional ribonucleoprotein particle. Extra-ribosomal protein factors play a fundamental role in the efficiency and efficacy of ribosomal subunit biogenesis. A paucity of data on intermediate steps, multiple and overlapping pathways, and the puzzling number of functions that extra-ribosomal proteins appear to play in vivo make unraveling the formation of this macromolecular assemblage difficult. In this review, we outline with examples the multinodal landscape of factor-assisted mechanisms that influence ribosome synthesis in bacteria. We discuss in detail late-stage events that mediate correct ribosome formation and the transition to translation initiation and thereby ensure high-fidelity protein synthesis.
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Regulation of Host-Pathogen Interactions via the Ubiquitin System
Vol. 76 (2022), pp. 211–233More LessUbiquitination is a posttranslational modification that regulates a multitude of cellular functions. Pathogens, such as bacteria and viruses, have evolved sophisticated mechanisms that evade or counteract ubiquitin-dependent host responses, or even exploit the ubiquitin system to their own advantage. This is largely done by numerous pathogen virulence factors that encode E3 ligases and deubiquitinases, which are often used as weapons in pathogen–host cell interactions. Moreover, upon pathogen attack, host cellular signaling networks undergo major ubiquitin-dependent changes to protect the host cell, including coordination of innate immunity, remodeling of cellular organelles, reorganization of the cytoskeleton, and reprogramming of metabolic pathways to restrict growth of the pathogen. Here we provide mechanistic insights into ubiquitin regulation of host-pathogen interactions and how it affects bacterial and viral pathogenesis and the organization and response of the host cell.
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Signal Transduction Network Principles Underlying Bacterial Collective Behaviors
Vol. 76 (2022), pp. 235–257More LessBacteria orchestrate collective behaviors and accomplish feats that would be unsuccessful if carried out by a lone bacterium. Processes undertaken by groups of bacteria include bioluminescence, biofilm formation, virulence factor production, and release of public goods that are shared by the community. Collective behaviors are controlled by signal transduction networks that integrate sensory information and transduce the information internally. Here, we discuss network features and mechanisms that, even in the face of dramatically changing environments, drive precise execution of bacterial group behaviors. We focus on representative quorum-sensing and second-messenger cyclic dimeric GMP (c-di-GMP) signal relays. We highlight ligand specificity versus sensitivity, how small-molecule ligands drive discrimination of kin versus nonkin, signal integration mechanisms, single-input sensory systems versus coincidence detectors, and tuning of input-output dynamics via feedback regulation. We summarize how different features of signal transduction systems allow groups of bacteria to successfully interpret and collectively react to dynamically changing environments.
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Function of the Omp85 Superfamily of Outer Membrane Protein Assembly Factors and Polypeptide Transporters
Vol. 76 (2022), pp. 259–279More LessThe Omp85 protein superfamily is found in the outer membrane (OM) of all gram-negative bacteria and eukaryotic organelles of bacterial origin. Members of the family catalyze both the membrane insertion of β-barrel proteins and the translocation of proteins across the OM. Although the mechanism(s) by which these proteins function is unclear, striking new insights have emerged from recent biochemical and structural studies. In this review we discuss the entire Omp85 superfamily but focus on the function of the best-studied member, BamA, which is an essential and highly conserved component of the bacterial barrel assembly machinery (BAM). Because BamA has multiple functions that overlap with those of other Omp85 proteins, it is likely the prototypical member of the Omp85 superfamily. Furthermore, BamA has become a protein of great interest because of the recent discovery of small-molecule inhibitors that potentially represent an important new class of antibiotics.
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Mining Fatty Acid Biosynthesis for New Antimicrobials
Vol. 76 (2022), pp. 281–304More LessAntibiotic resistance is a serious public health concern, and new drugs are needed to ensure effective treatment of many bacterial infections. Bacterial type II fatty acid synthesis (FASII) is a vital aspect of bacterial physiology, not only for the formation of membranes but also to produce intermediates used in vitamin production. Nature has evolved a repertoire of antibiotics inhibiting different aspects of FASII, validating these enzymes as potential targets for new antibiotic discovery and development. However, significant obstacles have been encountered in the development of FASII antibiotics, and few FASII drugs have advanced beyond the discovery stage. Most bacteria are capable of assimilating exogenous fatty acids. In some cases they can dispense with FASII if fatty acids are present in the environment, making the prospects for identifying broad-spectrum drugs against FASII targets unlikely. Single-target, pathogen-specific FASII drugs appear the best option, but a major drawback to this approach is the rapid acquisition of resistance via target missense mutations. This complication can be mitigated during drug development by optimizing the compound design to reduce the potential impact of on-target missense mutations at an early stage in antibiotic discovery. The lessons learned from the difficulties in FASII drug discovery that have come to light over the last decade suggest that a refocused approach to designing FASII inhibitors has the potential to add to our arsenal of weapons to combat resistance to existing antibiotics.
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On the Mechanistic Basis of Killer Meiotic Drive in Fungi
Vol. 76 (2022), pp. 305–323More LessSpore killers are specific genetic elements in fungi that kill sexual spores that do not contain them. A range of studies in the last few years have provided the long-awaited first insights into the molecular mechanistic aspects of spore killing in different fungal models, including both yeast-forming and filamentous Ascomycota. Here we describe these recent advances, focusing on the wtf system in the fission yeast Schizosaccharomyces pombe; the Sk spore killers of Neurospora species; and two spore-killer systems in Podospora anserina, Spok and [Het-s]. The spore killers appear thus far mechanistically unrelated. They can involve large genomic rearrangements but most often rely on the action of just a single gene. Data gathered so far show that the protein domains involved in the killing and resistance processes differ among the systems and are not homologous. The emerging picture sketched by these studies is thus one of great mechanistic and evolutionary diversity of elements that cheat during meiosis and are thereby preferentially inherited over sexual generations.
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Oxygenases as Powerful Weapons in the Microbial Degradation of Pesticides
Vol. 76 (2022), pp. 325–348More LessOxygenases, which catalyze the reductive activation of O2 and incorporation of oxygen atoms into substrates, are widely distributed in aerobes. They function by switching the redox states of essential cofactors that include flavin, heme iron, Rieske non-heme iron, and Fe(II)/α-ketoglutarate. This review summarizes the catalytic features of flavin-dependent monooxygenases, heme iron–dependent cytochrome P450 monooxygenases, Rieske non-heme iron–dependent oxygenases, Fe(II)/α-ketoglutarate-dependent dioxygenases, and ring-cleavage dioxygenases, which are commonly involved in pesticide degradation. Heteroatom release (hydroxylation-coupled hetero group release), aromatic/heterocyclic ring hydroxylation to form ring-cleavage substrates, and ring cleavage are the main chemical fates of pesticides catalyzed by these oxygenases. The diversity of oxygenases, specificities for electron transport components, and potential applications of oxygenases are also discussed. This article summarizes our current understanding of the catalytic mechanisms of oxygenases and a framework for distinguishing the roles of oxygenases in pesticide degradation.
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Wrapped Up: The Motility of Polarly Flagellated Bacteria
Vol. 76 (2022), pp. 349–367More LessA huge number of bacterial species are motile by flagella, which allow them to actively move toward favorable environments and away from hazardous areas and to conquer new habitats. The general perception of flagellum-mediated movement and chemotaxis is dominated by the Escherichia coli paradigm, with its peritrichous flagellation and its famous run-and-tumble navigation pattern, which has shaped the view on how bacteria swim and navigate in chemical gradients. However, a significant amount—more likely the majority—of bacterial species exhibit a (bi)polar flagellar localization pattern instead of lateral flagella. Accordingly, these species have evolved very different mechanisms for navigation and chemotaxis. Here, we review the earlier and recent findings on the various modes of motility mediated by polar flagella.
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Genomic Approaches to Antifungal Drug Target Identification and Validation
Vol. 76 (2022), pp. 369–388More LessThe last several decades have witnessed a surge in drug-resistant fungal infections that pose a serious threat to human health. While there is a limited arsenal of drugs that can be used to treat systemic infections, scientific advances have provided renewed optimism for the discovery of novel antifungals. The development of chemical-genomic assays using Saccharomyces cerevisiae has provided powerful methods to identify the mechanism of action of molecules in a living cell. Advances in molecular biology techniques have enabled complementary assays to be developed in fungal pathogens, including Candida albicans and Cryptococcus neoformans. These approaches enable the identification of target genes for drug candidates, as well as genes involved in buffering drug target pathways. Here, we examine yeast chemical-genomic assays and highlight how such resources can be utilized to predict the mechanisms of action of compounds, to study virulence attributes of diverse fungal pathogens, and to bolster the antifungal pipeline.
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Accelerated Evolution by Diversity-Generating Retroelements
Vol. 76 (2022), pp. 389–411More LessDiversity-generating retroelements (DGRs) create vast amounts of targeted, functional diversity by facilitating the rapid evolution of ligand-binding protein domains. Thousands of DGRs have been identified in bacteria, archaea, and their respective viruses. They are broadly distributed throughout the microbial world, with enrichment observed in certain taxa and environments. The diversification machinery works through a novel mechanism termed mutagenic retrohoming, whereby nucleotide sequence information is copied from an invariant DNA template repeat (TR) into an RNA intermediate, selectively mutagenized at TR adenines during cDNA synthesis by a DGR-encoded reverse transcriptase, and transferred to a variable repeat (VR) region within a variable-protein gene (54). This unidirectional flow of information leaves TR-DNA sequences unmodified, allowing for repeated rounds of mutagenic retrohoming to optimize variable-protein function. DGR target genes are often modular and can encode one or more of a wide variety of discrete functional domains appended to a diversifiable ligand-binding motif. Bacterial variable proteins often localize to cellsurfaces, although a subset appear to be cytoplasmic, while phage-encoded DGRs commonly diversify tail fiber–associated receptor-binding proteins. Here, we provide a comprehensive review of the mechanism and consequences of accelerated protein evolution by these unique and beneficial genetic elements.
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Regulation of Biofilm Exopolysaccharide Biosynthesis and Degradation in Pseudomonas aeruginosa
Vol. 76 (2022), pp. 413–433More LessMicrobial communities enmeshed in a matrix of macromolecules, termed as biofilms, are the natural setting of bacteria. Exopolysaccharide is a critical matrix component of biofilms. Here, we focus on biofilm matrix exopolysaccharides in Pseudomonas aeruginosa. This opportunistic pathogen can adapt to a wide range of environments and can form biofilms or aggregates in a variety of surfaces or environments, such as the lungs of people with cystic fibrosis, catheters, wounds, and contact lenses. The ability to synthesize multiple exopolysaccharides is one of the advantages that facilitate bacterial survival in different environments. P. aeruginosa can produce several exopolysaccharides, including alginate, Psl, Pel, and lipopolysaccharide. In this review, we highlight the roles of each exopolysaccharide in P. aeruginosa biofilm development and how bacteria coordinate the biosynthesis of multiple exopolysaccharides and bacterial motility. In addition, we present advances in antibiofilm strategies targeting matrix exopolysaccharides, with a focus on glycoside hydrolases.
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Translating Microbiome Research From and To the Clinic
Vol. 76 (2022), pp. 435–460More LessExtensive research has elucidated the influence of the gut microbiota on human health and disease susceptibility and resistance. We review recent clinical and laboratory-based experimental studies associating the gut microbiota with certain human diseases. We also highlight ongoing translational advances that manipulate the gut microbiota to treat human diseases and discuss opportunities and challenges in translating microbiome research from and to the bedside.
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The Impact of RNA-DNA Hybrids on Genome Integrity in Bacteria
Vol. 76 (2022), pp. 461–480More LessDuring the essential processes of DNA replication and transcription, RNA-DNA hybrid intermediates are formed that pose significant risks to genome integrity when left unresolved. To manage RNA-DNA hybrids, all cells rely on RNase H family enzymes that specifically cleave the RNA portion of the many different types of hybrids that form in vivo. Recent experimental advances have provided new insight into how RNA-DNA hybrids form and the consequences to genome integrity that ensue when persistent hybrids remain unresolved. Here we review the types of RNA-DNA hybrids, including R-loops, RNA primers, and ribonucleotide misincorporations, that form during DNA replication and transcription and discuss how each type of hybrid can contribute to genome instability in bacteria. Further, we discuss how bacterial RNase HI, HII, and HIII and bacterial FEN enzymes contribute to genome maintenance through the resolution of hybrids.
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Horizontal Gene Transfer in Archaea—From Mechanisms to Genome Evolution
Vol. 76 (2022), pp. 481–502More LessArchaea remains the least-studied and least-characterized domain of life despite its significance not just to the ecology of our planet but also to the evolution of eukaryotes. It is therefore unsurprising that research into horizontal gene transfer (HGT) in archaea has lagged behind that of bacteria. Indeed, several archaeal lineages may owe their very existence to large-scale HGT events, and thus understanding both the molecular mechanisms and the evolutionary impact of HGT in archaea is highly important. Furthermore, some mechanisms of gene exchange, such as plasmids that transmit themselves via membrane vesicles and the formation of cytoplasmic bridges that allows transfer of both chromosomal and plasmid DNA, may be archaea-specific. This review summarizes what we know about HGT in archaea, and the barriers that restrict it, highlighting exciting recent discoveries and pointing out opportunities for future research.
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Mechanisms Underlying Vibrio cholerae Biofilm Formation and Dispersion
Vol. 76 (2022), pp. 503–532More LessBiofilms are a widely observed growth mode in which microbial communities are spatially structured and embedded in a polymeric extracellular matrix. Here, we focus on the model bacterium Vibrio cholerae and summarize the current understanding of biofilm formation, including initial attachment, matrix components, community dynamics, social interactions, molecular regulation, and dispersal. The regulatory network that orchestrates the decision to form and disperse from biofilms coordinates various environmental inputs. These cues are integrated by several transcription factors, regulatory RNAs, and second-messenger molecules, including bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP). Through complex mechanisms, V. cholerae weighs the energetic cost of forming biofilms against the benefits of protection and social interaction that biofilms provide.
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Compartmentalization of RNA Degradosomes in Bacteria Controls Accessibility to Substrates and Ensures Concerted Degradation of mRNA to Nucleotides
Vol. 76 (2022), pp. 533–552More LessRNA degradosomes are multienzyme complexes composed of ribonucleases, RNA helicases, and metabolic enzymes. RNase E–based degradosomes are widespread in Proteobacteria. The Escherichia coli RNA degradosome is sequestered from transcription in the nucleoid and translation in the cytoplasm by localization to the inner cytoplasmic membrane, where it forms short-lived clusters that are proposed to be sites of mRNA degradation. In Caulobacter crescentus, RNA degradosomes localize to ribonucleoprotein condensates in the interior of the cell [bacterial ribonucleoprotein-bodies (BR-bodies)], which have been proposed to drive the concerted degradation of mRNA to nucleotides. The turnover of mRNA in growing cells is important for maintaining pools of nucleotides for transcription and DNA replication.Membrane attachment of the E. coli RNA degradosome is necessary to avoid wasteful degradation of intermediates in ribosome assembly. Sequestering RNA degradosomes to C. crescentus BR-bodies, which exclude structured RNA, could have a similar role in protecting intermediates in ribosome assembly from degradation.
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Anaerobic Degradation of Alkanes by Marine Archaea
Vol. 76 (2022), pp. 553–577More LessAlkanes are saturated apolar hydrocarbons that range from their simplest form, methane, to high-molecular-weight compounds. Although alkanes were once considered biologically recalcitrant under anaerobic conditions, microbiological investigations have now identified several microbial taxa that can anaerobically degrade alkanes. Here we review recent discoveries in the anaerobic oxidation of alkanes with a specific focus on archaea that use specific methyl coenzyme M reductases to activate their substrates. Our understanding of the diversity of uncultured alkane-oxidizing archaea has expanded through the use of environmental metagenomics and enrichment cultures of syntrophic methane-, ethane-, propane-, and butane-oxidizing marine archaea with sulfate-reducing bacteria. A recently cultured group of archaea directly couples long-chain alkane degradation with methane formation, expanding the range of substrates used for methanogenesis. This article summarizes the rapidly growing knowledge of the diversity, physiology, and habitat distribution of alkane-degrading archaea.
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Metabolic Enabling and Detoxification by Mammalian Gut Microbes
Vol. 76 (2022), pp. 579–596More LessThe longstanding interactions between mammals and their symbionts enable thousands of mammal species to consume herbivorous diets. The microbial communities in mammals degrade both plant fiber and toxins. Microbial toxin degradation has been repeatedly documented in domestic ruminants, but similar work in wild mammals is more limited due to constraints on sampling and manipulating the microbial communities in these species. In this review, we briefly describe the toxins commonly encountered in mammalian diets, major classes of biotransformation enzymes in microbes and mammals, and the gut chambers that house symbiotic microbes. We next examine evidence for microbial detoxification in domestic ruminants before providing case studies on microbial toxin degradation in both foregut- and hindgut-fermenting wild mammals. We end by discussing species that may be promising for future investigations, and the advantages and limitations of approaches currently available for studying degradation of toxins by mammalian gut microbes.
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The Making of a Heterocyst in Cyanobacteria
Vol. 76 (2022), pp. 597–618More LessHeterocyst differentiation that occurs in some filamentous cyanobacteria, such as Anabaena sp. PCC 7120, provides a unique model for prokaryotic developmental biology. Heterocyst cells are formed in response to combined-nitrogen deprivation and possess a microoxic environment suitable for nitrogen fixation following extensive morphological and physiological reorganization. A filament of Anabaena is a true multicellular organism, as nitrogen and carbon sources are exchanged among different cells and cell types through septal junctions to ensure filament growth. Because heterocysts are terminally differentiated cells and unable to divide, their activity is an altruistic behavior dedicated to providing fixed nitrogen for neighboring vegetative cells. Heterocyst development is also a process of one-dimensional pattern formation, as heterocysts are semiregularly intercalated among vegetative cells. Morphogens form gradients along the filament and interact with each other in a fashion that fits well into the Turing model, a mathematical framework to explain biological pattern formation.
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How Apicomplexa Parasites Secrete and Build Their Invasion Machinery
Vol. 76 (2022), pp. 619–640More LessApicomplexa are obligatory intracellular parasites that sense and actively invade host cells. Invasion is a conserved process that relies on the timely and spatially controlled exocytosis of unique specialized secretory organelles termed micronemes and rhoptries. Microneme exocytosis starts first and likely controls the intricate mechanism of rhoptry secretion. To assemble the invasion machinery, micronemal proteins—associated with the surface of the parasite—interact and form complexes with rhoptry proteins, which in turn are targeted into the host cell. This review covers the molecular advances regarding microneme and rhoptry exocytosis and focuses on how the proteins discharged from these two compartments work in synergy to drive a successful invasion event. Particular emphasis is given to the structure and molecular components of the rhoptry secretion apparatus, and to the current conceptual framework of rhoptry exocytosis that may constitute an unconventional eukaryotic secretory machinery closely related to the one described in ciliates.
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The Small-Molecule Language of Dynamic Microbial Interactions
Vol. 76 (2022), pp. 641–660More LessAlthough microbes are routinely grown in monocultures in the laboratory, they are almost never encountered as single species in the wild. Our ability to detect and identify new microorganisms has advanced significantly in recent years, but our understanding of the mechanisms that mediate microbial interactions has lagged behind. What makes this task more challenging is that microbial alliances can be dynamic, consisting of multiple phases. The transitions between phases, and the interactions in general, are often mediated by a chemical language consisting of small molecules, also referred to as secondary metabolites or natural products. In this microbial lexicon, the molecules are like words and through their effects on recipient cells they convey meaning. The current review highlights three dynamic microbial interactions in which some of the words and their meanings have been characterized, especially those that mediate transitions in selected multiphasic associations. These systems provide insights into the principles that govern microbial symbioses and a playbook for interrogating similar associations in diverse ecological niches.
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Evolution of Tuberculosis Pathogenesis
Vol. 76 (2022), pp. 661–680More LessMycobacterium tuberculosis is a globally distributed, lethal pathogen of humans. The virulence armamentarium of M. tuberculosis appears to have been developed on a scaffold of antiphagocytic defenses found among diverse, mostly free-living species of Mycobacterium. Pathoadaptation was further aided by the modularity, flexibility, and interactivity characterizing mycobacterial effectors and their regulators. During emergence of M. tuberculosis, novel genetic material was acquired, created, and integrated with existing tools. The major mutational mechanisms underlying these adaptations are discussed in this review, with examples. During its evolution, M. tuberculosis lost the ability and/or opportunity to engage in lateral gene transfer, but despite this it has retained the adaptability that characterizes mycobacteria. M. tuberculosis exemplifies the evolutionary genomic mechanisms underlying adoption of the pathogenic niche, and studies of its evolution have uncovered a rich array of discoveries about how new pathogens are made.
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Emerging Concepts in Cholera Vaccine Design
Vol. 76 (2022), pp. 681–702More LessCholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae and constitutes a significant public health threat in many areas of the world. V. cholerae infection elicits potent and long-lasting immunity, and efforts to develop cholera vaccines have been ongoing for more than a century. Currently available inactivated two-dose oral cholera vaccines are increasingly deployed to both prevent and actively curb cholera outbreaks, and they are key components of the global effort to eradicate cholera. However, these killed whole-cell vaccines have several limitations, and a variety of new oral and nonoral cholera vaccine platforms have recently been developed. Here, we review emerging concepts in cholera vaccine design and implementation that have been driven by insights from human and animal studies. As a prototypical vaccine-preventable disease, cholera continues to be an excellent target for the development and application of cutting-edge technologies and platforms that may transform vaccinology.
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Harnessing the Immune Response to Fungal Pathogens for Vaccine Development
Vol. 76 (2022), pp. 703–726More LessInvasive fungal infections are emerging diseases that kill over 1.5 million people per year worldwide. With the increase of immunocompromised populations, the incidence of invasive fungal infections is expected to continue to rise. Vaccines for viral and bacterial infectious diseases have had a transformative impact on human health worldwide. However, no fungal vaccines are currently in clinical use. Recently, interest in fungal vaccines has grown significantly. One Candida vaccine has completed phase 2 clinical trials, and research on vaccines against coccidioidomycosis continues to advance. Additionally, multiple groups have discovered various Cryptococcus mutant strains that promote protective responses to subsequent challenge in mouse models. There has also been progress in antibody-mediated fungal vaccines. In this review, we highlight recent fungal vaccine research progress, outline the wealth of data generated, and summarize current research for both fungal biology and immunology studies relevant to fungal vaccine development. We also review technological advancements in vaccine development and highlight the future prospects of a human vaccine against invasive fungal infections.
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Diversity and Evolution of Methane-Related Pathways in Archaea
Vol. 76 (2022), pp. 727–755More LessMethane is one of the most important greenhouse gases on Earth and holds an important place in the global carbon cycle. Archaea are the only organisms that use methanogenesis to produce energy and rely on the methyl–coenzyme M reductase complex (Mcr). Over the last decade, new results have significantly reshaped our view of the diversity of methane-related pathways in the Archaea. Many new lineages that synthesize or use methane have been identified across the whole archaeal tree, leading to a greatly expanded diversity of substrates and mechanisms. In this review, we present the state of the art of these advances and how they challenge established scenarios of the origin and evolution of methanogenesis, and we discuss the potential trajectories that may have led to this strikingly wide range of metabolisms.
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Malassezia: A Commensal, Pathogen, and Mutualist of Human and Animal Skin
Vol. 76 (2022), pp. 757–782More LessIdentified in the late nineteenth century as a single species residing on human skin, Malassezia is now recognized as a diverse genus comprising 18 species inhabiting not only skin but human gut, hospital environments, and even deep-sea sponges. All cultivated Malassezia species are lipid dependent, having lost genes for lipid synthesis and carbohydrate metabolism. The surging interest in Malassezia results from development of tools to improve sampling, culture, identification, and genetic engineering, which has led to findings implicating it in numerous skin diseases, Crohn disease, and pancreatic cancer. However, it has become clear that Malassezia plays a multifaceted role in human health, with mutualistic activity in atopic dermatitis and a preventive effect against other skin infections due to its potential to compete with skin pathogens such as Candida auris. Improved understanding of complex microbe-microbe and host-microbe interactions will be required to define Malassezia’s role in human and animal health and disease so as to design targeted interventions.
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Previous Volumes
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Volume 77 (2023)
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Volume 76 (2022)
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Volume 75 (2021)
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Volume 74 (2020)
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Volume 73 (2019)
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Volume 72 (2018)
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Volume 71 (2017)
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Volume 70 (2016)
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Volume 69 (2015)
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Volume 68 (2014)
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Volume 67 (2013)
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Volume 66 (2012)
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Volume 65 (2011)
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Volume 64 (2010)
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Volume 63 (2009)
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Volume 62 (2008)
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Volume 61 (2007)
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Volume 60 (2006)
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Volume 50 (1996)
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Volume 49 (1995)
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Volume 46 (1992)
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Volume 45 (1991)
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Volume 27 (1973)
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Volume 26 (1972)
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Volume 2 (1948)
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Volume 1 (1947)
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Volume 0 (1932)