Microbiology and Molecular Biology Reviews最新文献

SUMMARYKlebsiella pneumoniae is a gram-negative species, whose isolates are found in the environment and as commensals in the human gastrointestinal tract. This bacterium is among the leading causes of a range of nosocomial and community-acquired infections, particularly in immunocompromised individuals, where it can give rise to pneumonia, urinary tract infections, septicemia, and liver abscesses. Treatment of K. pneumoniae infections is compromised by the emergence of isolates producing carbapenemase and extended-spectrum β-lactamase enzymes, making it a high priority for new therapeutic approaches including vaccination and immunoprophylaxis. One potential target for these strategies is the O-antigen polysaccharide component of lipopolysaccharides, which are important virulence determinants for K. pneumoniae. Consideration of immunotherapeutic opportunities requires a comprehensive and fundamental understanding of O-polysaccharide structures, distribution of particular O serotypes in clinical isolates, and the potential for antigenic diversification. The number of recognized K. pneumoniae O-polysaccharide antigens has varied over time, complicated by the observation that some examples share similar structural (and potentially antigenically cross-reactive) elements, and by the existence of genetic loci for which corresponding O-polysaccharide structures have yet to be determined. Here, we provide a comprehensive integration of the current carbohydrate structures and genetic information, together with a proposal for an updated classification system for K. pneumoniae O-antigens, that is being implemented in Kaptive for molecular serotyping. The accumulated insight into O-polysaccharide assembly pathways is used to describe the molecular basis for O-antigen diversity in K. pneumoniae.

SUMMARYOver the past 25 years, there has been an increasing number of mammalian (including human) infections caused by avian influenza A viruses that resulted in mild to severe illnesses. These viruses typically did not spread between mammals through aerosols in nature or in experimental settings. However, recently, this has changed, with several avian influenza A viruses exhibiting aerosol transmissibility among mammals, indicating that these viruses may pose a greater pandemic risk. In this review, we examine the current situation and discuss the mutations that may be necessary for avian influenza A viruses to efficiently replicate in mammals and transmit among them via aerosols.

SUMMARYThe bacterial cytoplasmic membrane, consisting of roughly equal proportions of proteins and lipids, plays a crucial role in cellular growth, metabolism, and maintaining the cytoplasmic boundary. It is a dynamic, fluid matrix that separates intracellular compartments, where lipids and proteins coexist in a highly organized yet flexible arrangement. Membrane fluidity, defined as the inverse of viscosity, determines how rapidly molecules diffuse within the membrane at a given temperature. This property is vital for protein mobility and biomolecular interactions. Structurally, the membrane primarily comprises a lamellar lipid bilayer, with glycerophospholipids and fatty acids forming its core framework. In Bacillus subtilis, a key model organism for studying gram-positive bacterial physiology, major membrane lipids include phospholipids, glycolipids, and lipoteichoic acids, the latter anchored to diacylglycerol glycolipids. This review examines the synthesis and regulation of membrane lipids in B. subtilis, with a focus on fatty acid biosynthesis, its diversification, and post-synthetic modifications such as desaturation. It also explores the production of phosphatidic acid and the integration of fatty acid and phospholipid biosynthesis. We review the well-characterized pathway of cold-induced membrane lipid modification in B. subtilis, arguably the best-studied model system for temperature sensing. This pathway is tightly linked to transcriptional responses triggered by changes in bilayer viscosity, detected by a membrane-associated thermosensor. Finally, this review highlights the importance of fatty acid biosynthesis in B. subtilis differentiation and its contributions to the production of biotin and lipoic acid, two universal cofactors essential for fatty acid synthesis and intermediary metabolism.

SUMMARYChagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi (Tc), infecting 6-7 million people. It is transmitted by insect vectors, orally, through infected tissues, or congenitally. Tc infection can progress toward chronic cardiac and/or digestive severe and fatal CD in 20%-40% of patients. Tc exhibits an important genetic and phenotypic intraspecies diversity and a preponderant clonal population structure. The impact of multiclonal coinfections has been little studied in CD patients. Relationships between the currently used discrete typing unit (DTU)-based classification of Tc lineages and the occurrence of the different clinical forms of CD, its congenital transmission, as well as the efficacy of trypanocidal molecules (benznidazole and nifurtimox) could not be established. In this review, we revisit the different aspects of Tc diversity and analyze the impact of infections with multiple clones and their variants on the dynamic and pathogenesis of CD and its maternal-fetal transmission. We propose to call "cruziome" all the Tc clones and their variants infecting a given host and provide strong evidence that (i) multiclonal Tc infections are likely the rule rather than the exception; (ii) each "cruziome" is associated with a unique combination of virulence factors, tissular tropisms, and host immune responses; (iii) accordingly, some particularly harmful "cruziomes" likely trigger the occurrence and progression of CD and might also favor the congenital transmission of parasites. We propose that our concept of "cruziome" should be taken into consideration because of its practical consequences in epidemiological studies, laboratory diagnosis, clinical management, and treatment of CD.

SUMMARYAdvances in modern medical therapies for many previously intractable human diseases have improved patient outcomes. However, successful disease treatment outcomes are often prevented due to invasive fungal infections caused by the environmental mold Aspergillus fumigatus. As contemporary antifungal therapies have not experienced the same robust advances as other medical therapies, defining mechanisms of A. fumigatus disease initiation and progression remains a critical research priority. To this end, the World Health Organization recently identified A. fumigatus as a research priority human fungal pathogen and the Centers for Disease Control has highlighted the emergence of triazole-resistant A. fumigatus isolates. The expansion in the diversity of host populations susceptible to aspergillosis and the complex and dynamic A. fumigatus genotypic and phenotypic diversity call for a reinvigorated assessment of aspergillosis pathobiological and drug-susceptibility mechanisms. Here, we summarize recent advancements in the field and discuss challenges in our understanding of A. fumigatus heterogeneity and its pathogenesis in diverse host populations.

SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole. During colony differentiation, an almost infinite number of ecological and physiological population-forming forces are at work, creating complex, intricate colony structures with divergent functions. Understanding the assembly and dynamics of such populations requires resolving individual cells or cell groups within such macroscopic structures. Addressing how each cell contributes to the collective action requires pushing the resolution boundaries of key technologies that will be presented in this review. In particular, single-cell techniques provide powerful tools for studying bacterial multicellularity with unprecedented spatial and temporal resolution. These advancements include novel microscopic techniques, mass spectrometry imaging, flow cytometry, spatial transcriptomics, single-bacteria RNA sequencing, and the integration of spatiotemporal transcriptomics with microscopy, alongside advanced microfluidic cultivation systems. This review encourages exploring the synergistic potential of the new technologies in the study of bacterial multicellularity, with a particular focus on individuals in differentiated bacterial biofilms (colonies). It highlights how resolving population structures at the single-cell level and understanding their respective functions can elucidate the overarching functions of bacterial multicellular populations.

SUMMARYEnterococcus faecalis is a significant resident of the gastrointestinal tract of most animals, including humans. Although generally non-pathogenic in healthy hosts, this microbe is adept at the exploitation of compromises in host immune functions, resulting in life-threatening opportunistic infections whose treatments are complicated by a high degree of intrinsic and acquired resistance to antimicrobial chemotherapy. Historically, progress in enterococcal research was limited by a lack of experimental models that replicate natural infection pathways and the relevance of in vitro studies to the natural biology of the organism. In this review, we summarize the history of enterococcal research during the 20th and early 21st centuries and describe more recent genetic and genomic tools and screens developed to address challenges in the field. We also describe how the results of recent studies reveal the importance of previously uncharacterized enterococcal genes, and we provide examples of interesting determinants that have emerged as important contributors to enterococcal biology. These factors may also serve as targets for future vaccines and chemotherapeutic agents to combat life-threatening hospital infections.

SUMMARYThe human malaria parasite Plasmodium falciparum is known for its ability to maintain lengthy infections that can extend for over a year. This property is derived from the parasite's capacity to continuously alter the antigens expressed on the surface of the infected red blood cell, thereby avoiding antibody recognition and immune destruction. The primary target of the immune system is an antigen called PfEMP1 that serves as a cell surface receptor and enables infected cells to adhere to the vascular endothelium and thus avoid filtration by the spleen. The parasite's genome encodes approximately 60 antigenically distinct forms of PfEMP1, each encoded by individual members of the multicopy var gene family. This provides the parasite with a repertoire of antigenic types that it systematically cycles through over the course of an infection, thereby maintaining an infection until the repertoire is exhausted. While this model of antigenic variation based on var gene switching explains the dynamics of acute infections in individuals with limited anti-malarial immunity, it fails to explain reports of chronic, asymptomatic infections that can last over a decade. Recent field studies have led to a re-evaluation of previous conclusions regarding the prevalence of chronic infections, and the application of new technologies has provided insights into the molecular mechanisms that enable chronic infections and how these processes evolved.

SUMMARYHuman coronaviruses cause a range of respiratory diseases, from the common cold (HCoV-229E, HCoV-NL63, HCoV-OC43, and SARS-CoV-2) to lethal pneumonia (SARS-CoV, SARS-CoV-2, and MERS-CoV). Coronavirus interactions with host innate immune antiviral responses are an important determinant of disease outcome. This review compares the host's innate response to different human coronaviruses. Host antiviral defenses discussed in this review include frontline defenses against respiratory viruses in the nasal epithelium, early sensing of viral infection by innate immune effectors, double-stranded RNA and stress-induced antiviral pathways, and viral antagonism of innate immune responses conferred by conserved coronavirus nonstructural proteins and genus-specific accessory proteins. The common cold coronaviruses HCoV-229E and -NL63 induce robust interferon signaling and related innate immune pathways, SARS-CoV and SARS-CoV-2 induce intermediate levels of activation, and MERS-CoV shuts down these pathways almost completely.