Annual review of microbiology最新文献

Human infectious diseases are unique in that the discovery of their environmental trigger, the microbe, was sufficient to drive the development of extraordinarily effective principles and tools for their prevention or cure. This unique medical prowess has outpaced, and perhaps even hindered, the development of scientific progress of equal magnitude in the biological understanding of infectious diseases. Indeed, the hope kindled by the germ theory of disease was rapidly subdued by the infection enigma, in need of a host solution, when it was realized that most individuals infected with most infectious agents continue to do well. The root causes of disease and death in the unhappy few remained unclear. While canonical approaches in vitro (cellular microbiology), in vivo (animal models), and in natura (clinical studies) analyzed the consequences of infection with a microbe, considered to be the cause of disease, in cells, tissues, or organisms seen as a uniform host, alternative approaches searched for preexisting causes of disease, particularly human genetic and immunological determinants in populations of diverse individuals infected with a trigger microbe.

Pore-forming toxins (PFTs) are released by one cell to directly inflict damage on another cell. Hosts use PFTs, including members of the membrane attack complex/perforin protein family, to fight infections and cancer, while bacteria and parasites deploy PFTs to promote infection. Apicomplexan parasites secrete perforin-like proteins as PFTs to egress from infected cells and traverse tissue barriers. Other protozoa, along with helminth parasites, utilize saposin-like PFTs prospectively for nutrient acquisition during infection. This review discusses seminal and more recent advances in understanding how parasite PFTs promote infection and describes how they are regulated and fulfill their roles without causing parasite self-harm. Although exciting progress has been made in defining mechanisms of pore formation by PFTs, many open questions remain to be addressed to gain additional key insights into these remarkable determinants of parasitic infections.

The major human spirochetal pathogens (Leptospira, Borrelia, and Treponema) are difficult to diagnose and lack vaccines to prevent infections. Infection by these spirochetes does not generate general protective immunity, allowing reinfection by different strains to occur. These stealth pathogens have uncommon physiology, pathogenesis, and clinical presentations and possess unique immune evasion mechanisms to facilitate their host adaptation and persistence. Collectively, host-spirochete interactions orchestrate systemic infections in a manner distinct from organ- and tissue-specific diseases caused by many bacterial pathogens. Difficulties in growing and genetic manipulation of infectious spirochetes have hindered the full understanding of their virulence factors despite decades to centuries of research. This article highlights the current understanding of the intricacies of spirochetal pathogenesis and diseases. Our comprehensive review of the progress versus gaps in knowledge lays a foundation for researchers to direct their studies toward the development of effective diagnostics and vaccines to protect patients from serious, chronic spirochetal diseases.

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.

The micronutrient iron is essential for phytoplankton growth due to its central role in a wide variety of key metabolic processes including photosynthesis and nitrate assimilation. As a result of scarce bioavailable iron in seawater, marine primary productivity is often iron-limited with future iron supplies remaining uncertain. Although evolutionary constraints resulted in high cellular iron requirements, phytoplankton evolved diverse mechanisms that enable uptake of multiple forms of iron, storage of iron over short and long timescales, and modulation of their iron requirement under stress. Genomics continues to increase our understanding of iron-related proteins that are homologous to those characterized in other model organisms, while recently, molecular and cell biology have been revealing unique genes and processes with connections to iron acquisition or use. Moreover, there are an increasing number of examples showing the interplay between iron uptake and extracellular processes such as boundary layer chemistry and microbial interactions.

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and size of a tail apparatus. We inventory the building blocks implicated in genome delivery and critically analyze putative mechanisms of genome ejection. Bacteriophage genome delivery into bacteria is a topic of growing interest, given the renaissance of phage therapy in Western medicine as a therapeutic alternative to face the antibiotic resistance crisis.

Arbuscular mycorrhizal fungi (AMF) are obligate mutualists that can enhance nutrition and growth of their plant hosts while providing protection against pathogens. AMF produce spores and hyphal networks that can carry thousands of nuclei in a continuous cytoplasm, with no evidence of sexual reproduction. This review examines the impact of genomic technologies on our view of AMF genetics and evolution. We highlight how the genetics, nuclear dynamics, and epigenetics of these prominent symbionts follow trends preserved in distant multinucleate fungal relatives. We also propose new avenues of research to improve our understanding of their nuclear biology and their intricate genetic interactions with plant hosts.

Fungal infections continue to represent a major threat to public health, particularly with the emergence of multidrug-resistant fungal pathogens. As part of the innate immune response, the host modulates the availability of metals as armament against pathogenic microbes, including fungi. The transition metals Fe, Cu, Zn, and Mn are essential micronutrients for all life forms, but when present in excess, these same metals are potent toxins. The host exploits the double-edged sword of these metals, and will either withhold metal micronutrients from pathogenic fungi or attack them with toxic doses. In response to these attacks, fungal pathogens cleverly adapt by modulating metal transport, metal storage, and usage of metals as cofactors for enzymes. Here we review the current state of understanding on Fe, Cu, Zn, and Mn at the host-fungal pathogen battleground and provide perspectives for future research, including a hope for new antifungals based on metals.

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.

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.