Annual review of microbiology最新文献

Envelope biogenesis and homeostasis in gram-negative bacteria are exceptionally intricate processes that require a multitude of periplasmic chaperones to ensure cellular survival. Remarkably, these chaperones perform diverse yet specialized functions entirely in the absence of external energy such as ATP, and as such have evolved sophisticated mechanisms by which their activities are regulated. In this article, we provide an overview of the predominant periplasmic chaperones that enable efficient outer membrane biogenesis and envelope homeostasis in Escherichia coli. We also discuss stress responses that act to combat unfolded protein stress within the cell envelope, highlighting the periplasmic chaperones involved and the mechanisms by which envelope homeostasis is restored.

Bacteria encode an arsenal of diverse systems that defend against phage infection. A common theme uniting many prevalent antiphage defense systems is the use of specialized nucleotide signals that function as second messengers to activate downstream effector proteins and inhibit viral propagation. In this article, we review the molecular mechanisms controlling nucleotide immune signaling in four major families of antiphage defense systems: CBASS, Pycsar, Thoeris, and type III CRISPR immunity. Analyses of the individual steps connecting phage detection, nucleotide signal synthesis, and downstream effector function reveal shared core principles of signaling and uncover system-specific strategies used to augment immune defense. We compare recently discovered mechanisms used by phages to evade nucleotide immune signaling and highlight convergent strategies that shape host-virus interactions. Finally, we explain how the evolutionary connection between bacterial antiphage defense and eukaryotic antiviral immunity defines fundamental rules that govern nucleotide-based immunity across all kingdoms of life.

Tackling the challenge created by antibiotic resistance requires understanding the mechanisms behind its evolution. Like any evolutionary process, the evolution of antimicrobial resistance (AMR) is driven by the underlying variation in a bacterial population and the selective pressures acting upon it. Importantly, both selection and variation will depend on the scale at which resistance evolution is considered (from evolution within a single patient to the host population level). While laboratory experiments have generated fundamental insights into the mechanisms underlying antibiotic resistance evolution, the technological advances in whole genome sequencing now allow us to probe antibiotic resistance evolution beyond the lab and directly record it in individual patients and host populations. Here we review the evolutionary forces driving antibiotic resistance at each of these scales, highlight gaps in our current understanding of AMR evolution, and discuss future steps toward evolution-guided interventions.

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.

Apicomplexan parasites are a group of eukaryotic protozoans with diverse biology that have affected human health like no other group of parasites. These obligate intracellular parasites rely on their cytoskeletal structures for giving them form, enabling them to replicate in unique ways and to migrate across tissue barriers. Recent progress in transgenesis and imaging tools allowed detailed insights into the components making up and regulating the actin and microtubule cytoskeleton as well as the alveolate-specific intermediate filament-like cytoskeletal network. These studies revealed interesting details that deviate from the cell biology of canonical model organisms. Here we review the latest developments in the field and point to a number of open questions covering the most experimentally tractable parasites: Plasmodium, the causative agent of malaria; Toxoplasma gondii, the causative agent of toxoplasmosis; and Cryptosporidium, a major cause of diarrhea.

The bacterial chemotaxis system is one of the best-understood cellular pathways and serves as the model for signal transduction systems. Most chemotaxis research has been conducted with transmembrane chemotaxis systems from Escherichia coli and has established paradigms of the system that were thought to be universal. However, emerging research has revealed that many bacteria possess alternative features of their chemotaxis system, demonstrating that these systems are likely more complex than previously assumed. Here, we compare the canonical chemotaxis system of E. coli with systems that diverge in supramolecular architecture, sensory mechanisms, and protein composition. The alternative features have likely evolved to accommodate chemical specificities of natural niches and cell morphologies. Collectively, these studies demonstrate that bacterial chemotaxis systems are a rapidly expanding field that offers many new opportunities to explore this exceedingly diverse system.

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.

Peptidoglycan (PGN) and associated surface structures such as secondary polymers and capsules have a central role in the physiology of bacteria. The exoskeletal PGN heteropolymer is the major determinant of cell shape and allows bacteria to withstand cytoplasmic turgor pressure. Thus, its assembly, expansion, and remodeling during cell growth and division need to be highly regulated to avoid compromising cell survival. Similarly, regulation of the assembly impacts bacterial cell shape; distinct shapes enhance fitness in different ecological niches, such as the host. Because bacterial cell wall components, in particular PGN, are exposed to the environment and unique to bacteria, these have been coopted during evolution by eukaryotes to detect bacteria. Furthermore, the essential role of the cell wall in bacterial survival has made PGN an important signaling molecule in the dialog between host and microbes and a target of many host responses. Millions of years of coevolution have resulted in a pivotal role for PGN fragments in shaping host physiology and in establishing a long-lasting symbiosis between microbes and the host. Thus, perturbations of this dialog can lead to pathologies such as chronic inflammatory diseases. Similarly, pathogens have devised sophisticated strategies to manipulate the system to enhance their survival and growth.

Bacterial cell growth and division require temporal and spatial coordination of multiple processes to ensure viability and morphogenesis. These mechanisms both determine and are determined by dynamic cellular structures and components, from within the cytoplasm to the cell envelope. The characteristic morphological changes during the cell cycle are largely driven by the architecture and mechanics of the cell wall. A constellation of proteins governs growth and division in Staphylococcus aureus, with counterparts also found in other organisms, alluding to underlying conserved mechanisms. Here, we review the status of knowledge regarding the cell cycle of this important pathogen and describe how this informs our understanding of the action of antibiotics and the specter of antimicrobial resistance.