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- Volume 76, 2022
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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Previous Volumes
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Volume 78 (2024)
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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 59 (2005)
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Volume 58 (2004)
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Volume 57 (2003)
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Volume 56 (2002)
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Volume 55 (2001)
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Volume 54 (2000)
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Volume 53 (1999)
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Volume 52 (1998)
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Volume 51 (1997)
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Volume 50 (1996)
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Volume 49 (1995)
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Volume 48 (1994)
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Volume 47 (1993)
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Volume 46 (1992)
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Volume 45 (1991)
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Volume 44 (1990)
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Volume 43 (1989)
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Volume 42 (1988)
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Volume 41 (1987)
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Volume 40 (1986)
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Volume 39 (1985)
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Volume 38 (1984)
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Volume 37 (1983)
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Volume 36 (1982)
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Volume 35 (1981)
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Volume 34 (1980)
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Volume 33 (1979)
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Volume 32 (1978)
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Volume 31 (1977)
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Volume 30 (1976)
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Volume 29 (1975)
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Volume 28 (1974)
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Volume 27 (1973)
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Volume 26 (1972)
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Volume 25 (1971)
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Volume 24 (1970)
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Volume 23 (1969)
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Volume 22 (1968)
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Volume 21 (1967)
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Volume 20 (1966)
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Volume 19 (1965)
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Volume 18 (1964)
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Volume 17 (1963)
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Volume 16 (1962)
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Volume 15 (1961)
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Volume 14 (1960)
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Volume 13 (1959)
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Volume 12 (1958)
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Volume 11 (1957)
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Volume 10 (1956)
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Volume 9 (1955)
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Volume 8 (1954)
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Volume 7 (1953)
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Volume 6 (1952)
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Volume 5 (1951)
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Volume 4 (1950)
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Volume 3 (1949)
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Volume 2 (1948)
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Volume 1 (1947)
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Volume 0 (1932)