Annual Review of Microbiology - Volume 78, 2024

A unique class of multimeric proteins made of covalently linked subunits known as pili, or fimbriae, are assembled and displayed on the gram-positive bacterial cell surface by a conserved transpeptidase enzyme named pilus-specific sortase. Sortase-assembled pili are produced by a wide range of gram-positive commensal and pathogenic bacteria inhabiting diverse niches such as the human oral cavity, gut, urogenital tract, and skin. These surface appendages serve many functions, including as molecular adhesins, immuno-modulators, and virulence determinants, that significantly contribute to both the commensal and pathogenic attributes of producer microbes. Intensive genetic, biochemical, physiological, and structural studies have been devoted to unveiling the assembly mechanism and functions, as well as the utility of these proteins in vaccine development and other biotechnological applications. We provide a comprehensive review of these topics and discuss the current status and future prospects of the field.

Staphylococcus aureus is a commensal of the skin and nares of humans as well as the causative agent of infections associated with significant mortality. The acquisition of antibiotic resistance traits complicates the treatment of such infections and has prompted the development of monoclonal antibodies. The selection of protective antigens is typically guided by studying the natural antibody responses to a pathogen. What happens when the pathogen masks these antigens and subverts adaptive responses, or when the pathogen inhibits or alters the effector functions of antibodies? S. aureus is constantly exposed to its human host and has evolved all these strategies. Here, we review how anti-S. aureus targets have been selected and how antibodies have been engineered to overcome the formidable immune evasive activities of this pathogen. We discuss the prospects of antibody-based therapeutics in the context of disease severity, immune competence, and history of past infections.

In contrast to the well-known DNA methylation of nucleobases, DNA phosphorothioate (PT) modification occurs in the DNA sugar-phosphate backbone. The non-bridging oxygen is replaced by a sulfur atom, which increases the nuclease tolerance of the DNA. In recent years, we have witnessed advances in understanding of PT modification enzymes, the features of PT modification across prokaryotic genomes, and PT-related physiological functions. Although only a small fraction of modifiable recognition sites across bacterial genomes undergo PT modification, enzymes such as DndFGH and SspE can use this modification as a recognition marker to differentiate between self- and non-self-DNA, thus destroying PT-lacking invasive DNA and preventing autoimmunity. We highlight the molecular mechanisms of PT modification–associated defense systems. We also describe notable applications of PT systems in the engineering of phage-resistant bacterial strains, RNA editing, and nucleic acid detection.

For more than 3.5 billion years, life experienced dramatic environmental extremes on Earth. These include shifts from oxygen-less to overoxygenated atmospheres and cycling between hothouse conditions and global glaciations. Meanwhile, an ecological revolution took place. Earth evolved from one dominated by microbial life to one containing the plants and animals that are most familiar today. Many key cellular features evolved early in the history of life, collectively defining the nature of our biosphere and underpinning human survival. Recent advances in molecular biology and bioinformatics have greatly improved our understanding of microbial evolution across deep time. However, the incorporation of molecular genetics, population biology, and evolutionary biology approaches into the study of Precambrian biota remains a significant challenge. This review synthesizes our current knowledge of early microbial life with an emphasis on ancient metabolisms. It also outlines the foundations of an emerging interdisciplinary area that integrates microbiology, paleobiology, and evolutionary synthetic biology to reconstruct ancient biological innovations.

Filamentous plant pathogens threaten global food security and ecosystem resilience. In recent decades, significant strides have been made in deciphering the molecular basis of plant–pathogen interactions, especially the interplay between pathogens’ molecular weaponry and hosts’ defense machinery. Stemming from interdisciplinary investigations into the infection cell biology of filamentous plant pathogens, recent breakthrough discoveries have provided a new impetus to the field. These advances include the biophysical characterization of a novel invasion mechanism (i.e., naifu invasion) and the unraveling of novel effector secretion routes. On the plant side, progress includes the identification of components of cellular networks involved in the uptake of intracellular effectors. This exciting body of research underscores the pivotal role of logistics management by the pathogen throughout the infection cycle, encompassing the precolonization stages up to tissue invasion. More insight into these logistics opens new avenues for developing environmentally friendly crop protection strategies in an era marked by an imperative to reduce the use of agrochemicals.

Dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur compounds with important roles in stress tolerance, chemotaxis, global carbon and sulfur cycling, and climate-active gas production. Diverse marine prokaryotes and eukaryotes produce DMSP via three known pathways (methylation, transamination, and decarboxylation) and metabolize DMSP via three further pathways (demethylation, cleavage, and oxidation). Over 20 key enzymes from these pathways have been identified that demonstrate the biodiversity and importance of DMSP cycling. The last dozen years have seen significant changes in our understanding of the enzymology and molecular mechanisms of these DMSP cycling enzymes through the application of biochemistry and structural biology. This has yielded more than 10 crystal structures and, in many cases, detailed explanations as to how and why organisms synthesis and metabolize DMSP. In this review, we describe recent progress in biochemical and mechanistic understandings of DMSP synthesis and metabolism, highlighting the important knowledge gleaned and current challenges that warrant further exploration.

Cyclic diguanylate (c-di-GMP) is a near-ubiquitous signaling molecule that regulates the motility-to-sessility transition in many bacterial species. Among the phenotypes influenced by c-di-GMP are biofilm formation, motility, cell cycle, and virulence. The hallmark phenotypes regulated by c-di-GMP—biofilm formation and motility—are key determinants of host–bacterial interactions. A large body of research has identified the roles of c-di-GMP in regulating phenotypes in culture. While numerous studies have investigated roles for c-di-GMP during the establishment and maintenance of pathogenic host–bacterial associations, considerably less attention has been devoted to defining the roles of c-di-GMP during beneficial and commensal associations. This review describes the known roles of c-di-GMP in regulating phenotypes that contribute to host colonization, with a focus on knowledge gaps and future prospects for examining c-di-GMP during beneficial colonization.

Gram-negative bacteria build an asymmetric outer membrane (OM), with lipopolysaccharides (LPS) and phospholipids (PLs) occupying the outer and inner leaflets, respectively. This distinct lipid arrangement is widely conserved within the Bacteria domain and confers strong protection against physical and chemical insults. The OM is physically separated from the inner membrane and the cytoplasm, where most cellular resources are located; therefore, the cell faces unique challenges in the assembly and maintenance of this asymmetric bilayer. Here, we present a framework for how gram-negative bacteria initially establish and continuously maintain OM lipid asymmetry, discussing the state-of-the-art knowledge of specialized lipid transport machines that place LPS and PLs directly into their corresponding leaflets in the OM, prevent excess PL accumulation and mislocalization, and correct any lipid asymmetry defects. We critically assess current studies, or the lack thereof, and highlight important future directions for research on OM lipid transport, homeostasis, and asymmetry.

Parasite manipulation of host behavior, as an effective strategy to establish transmission, has evolved multiple times across taxa, including fungi. Major strides have been made to propose molecular mechanisms that underlie manipulative parasite-host interactions including the manipulation of carpenter ant behavior by Ophiocordyceps. This research suggests that the secretion of parasite proteins and light-driven biological rhythms are likely involved in the infection and manipulation biology of Ophiocordyceps and other manipulating parasites. Here, we discuss research on Ophiocordyceps considering findings from other (fungal) parasites that either are relatively closely related (e.g., other insect- and plant-infecting Hypocreales) or also manipulate insect behavior (e.g., Entomophthorales). As such, this review aims to put forward this question: Are the mechanisms behind Ophiocordyceps manipulation and infection unique, or did they convergently evolve? From this discussion, we pose functional hypotheses about the infection biology of Ophiocordyceps that will need to be addressed in future studies.

Mycoviruses are widely distributed among various kinds of fungi. Over the past 10 years, more novel mycoviruses have been discovered with the use of high-throughput sequencing techniques, and research on mycoviruses has made fantastic progress, promoting our understanding of the diversity, classification, evolution, and ecology of the entire virosphere. Mycoviruses affect the biological and ecological functions of their hosts, for example, by suppressing or improving hosts’ virulence and reproduction ability, and subsequently affect the microbiological community where their hosts live; hence, we may develop mycoviruses to regulate the health of environments, plants, animals, and human beings. In this review, we introduce recently discovered mycoviruses from fungi of humans, animals, plants, and environments, and their diversity, evolution, and ecological characteristics. We also present the potential application of mycoviruses by describing the latest progress on using mycoviruses to control plant diseases. Finally, we discuss the main issues facing mycovirus research in the future.

The Dickeya genus comprises numerous pathogenic species that cause diseases in various crops, vegetables, and ornamental plants across the globe. The pathogens have become very widespread in recent years, and numerous newly identified Dickeya-associated plant diseases have been reported, which poses an immense threat to agricultural production and is a serious concern internationally. Evidence is accumulating that a diversity of hosts, environmental habitats, and climates seems to shape the abundance of Dickeya species in nature and the differentiation of pathogenic mechanisms. This review summarizes the latest findings on the genome diversity and pathogenic mechanisms of Dickeya spp., with a focus on the intricate virulence regulatory mechanisms mediated by quorum sensing and pathogen-host interkingdom communication systems.