Microbiology and Molecular Biology Reviews最新文献

SUMMARYInvasive fungal infections affect approximately 6.5 million people every year. These infections are frequently associated with high mortality rates, often exceeding 50%, even with antifungal therapy. Candida auris is a multidrug-resistant fungal pathogen that has a unique ability to grow and persist on human skin. Long-term skin colonization by C. auris is a significant medical concern because colonized patients may facilitate inter- and intra-hospital transmission of C. auris to other patients. Furthermore, C. auris-colonized patients are at risk of developing more serious systemic infections. The diagnosis of C. auris infections is often hampered by misidentification, leading to delays in starting appropriate antifungal therapy. Here, we summarize the global burden of candidiasis due to C. auris, antifungal drug resistance mechanisms, host and fungal factors affecting skin colonization, current diagnostic approaches, as well as current and future challenges to combat the spread of invasive fungal infections.

SUMMARYGram-negative bacteria frequently use efflux pumps of the resistance-nodulation-cell division (RND) superfamily to extrude various toxic compounds out of the cell. In particular, the hydrophobe-amphiphile efflux 1 (HAE1) and heavy-metal efflux (HME)-RND families are critical for the export of antimicrobials and heavy metals, respectively. These efflux pumps assemble as trimers at the inner membrane of the bacterium. In this review, structural and functional data are summarized for several of these HAE1 and HME-RND efflux pumps from work performed in our laboratory and others. Experimental results and analyses suggest that individual protomers of these efflux pumps within their respective trimer function independently and in an uncoordinated manner to export substrates. Based on these observations, a molecular mechanism that governs substrate recognition and extrusion for these membrane proteins is proposed. It is our hope that researchers in the field will continue to build upon these efforts and employ various biophysical and biochemical methodologies to fully understand the mechanistic basis of important RND efflux systems.

SUMMARYMost bacterial species possess two distinct types of glycosyltransferases (GTases or GTs), each with unique structural folds, which catalyze the addition of lipid II monomers to the anomeric reducing end of a growing glycan chain, ultimately forming β-1,4 glycosidic bonds. These bonds link the GlcNAc-MurNAc-peptide disaccharide subunits of the peptidoglycan (PG) polymer. The first type belongs to the carbohydrate-active enzyme (CAZy) GT51 family, which includes a lysozyme-like domain typically associated with a transpeptidase domain in bifunctional class A penicillin-binding proteins (aPBPs) and is occasionally found as a monofunctional GTase in certain bacteria. The second type, a C1-type GTase from the CAZy GT119 family, has a distinctly different structural fold and is composed of polytopic membrane proteins. These proteins also belong to the SEDS (shape, elongation, division, and sporulation) family and are characterized by 10 transmembrane segments and a large extracellular loop. In a single bacterial cell, multiple representatives of each family (aPBPs and SEDS) are typically present, often performing semi-redundant or distinct physiological functions. This review focuses on the structure-activity relationship of these two crucial PG GTases, the coordination between their GTase and the transpeptidase activities, and the regulatory mechanisms controlling these enzymes during cell growth and division within the elongasome and divisome complexes.

SUMMARYUnderstanding protein functions is crucial for interpreting microbial life; however, reliable function annotation remains a major challenge in computational biology. Despite significant advances in bioinformatics methods, ~30% of all bacterial and ~65% of all bacteriophage (phage) protein sequences cannot be confidently annotated. In this review, we examine state-of-the-art bioinformatics tools and methodologies for annotating bacterial and phage proteins, particularly those of unknown or poorly characterized function. We describe the process of identifying protein-coding regions and the systems to classify protein functionalities. Additionally, we explore a range of protein annotation methods, from traditional homology-based methods to cutting-edge machine learning models. In doing so, we provide a toolbox for confidently annotating previously unknown bacterial and phage proteins, advancing the discovery of novel functions and our understanding of microbial systems.

SUMMARYShiga toxin-producing Escherichia coli (STEC) strains cause diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS) in humans. HUS is a severe systemic illness that can affect individuals of all ages, especially children. There is no specific treatment for HUS, and interventions consist of supportive therapy. STEC infections occur worldwide, and severe illness may occur in sporadic cases or outbreaks. In 2023, STEC was the third most frequently reported zoonotic agent detected in foodborne outbreaks in the EU. In this manuscript, we have focused on STEC reservoirs, STEC contamination of foods, source attribution of STEC infections, and current discussions about the pathogenic potential of STEC strains present in foods. Considering that food contamination with STEC represents a serious threat to public health, that preventive strategies for STEC infection are critical, and natural antimicrobials have gained increasing interest, we also present thoroughly revised information about bacteriophages as a strategy for STEC control. We also discussed the main aspects of the performance of commercial and non-commercial bacteriophages on foods artificially contaminated with STEC.

SUMMARYThere is overwhelming evidence that antitumor CD8⁺ T cell responses can mediate effective tumor control. CD8⁺ T cell responses are quintessential defensive measures directed against categorically intracellular pathogens. It is thus intuitively obvious that viruses hold unique potential to mediate cancer in situ vaccination, the process whereby endogenous immune responses are provoked to empower antitumor immunity. Numerous attenuated viruses have been derived from diverse virus families and tested as intratumor "cancer virotherapies." However, the mechanistic understanding of how viruses mediate cancer in situ vaccination -including whether such attenuated viruses maintain the capacity to subvert antigen presentation and T cell priming, a common, defining feature of their wild-type precursors that may limit in situ vaccination, as well as the role of innate and adaptive antiviral immune responses in mediating overall therapy benefit-remains largely undefined. In this review, we provide a comprehensive overview of the molecular mechanisms, the unexpected benefit of profound attenuation, and the central role of both innate and adaptive antiviral immune responses in mediating polio virotherapy. In doing so, we aim to highlight the need for unraveling the enormous complexity and depth of virus:host interactions for devising rational strategies to leverage them for cancer immunotherapy.

SUMMARYNeurotropic viruses, a diverse group of pathogens targeting the central nervous system (CNS), utilize multiple mechanisms to invade this highly protected compartment. These include hematogenous spread, retrograde axonal transport, and Trojan horse strategies, enabling viral entry and dissemination. Once within the CNS, these viruses interact with resident immune cells such as microglia and astrocytes, triggering type I interferon responses critical for antiviral defense. However, neurotropic viruses employ immune evasion strategies, including inhibition of pattern recognition receptors (PRRs), suppression of interferon signaling, and disruption of antigen presentation pathways, allowing them to evade immune detection. These tactics facilitate their productive replication within the CNS and, in some cases, lead to persistent infections, often resulting in severe neurological consequences such as encephalitis and neuronal damage. This review explores these dynamic interactions and emphasizes future research needs, particularly in understanding virus-host interactions and developing targeted therapeutics to combat these pathogens effectively.

SUMMARYFungi use light as a signal for the regulation of development, to guide the growth of reproductive structures, and to protect the fungal cell from DNA damage produced by light and UV radiation. Light perception requires the activity of photoreceptors that relay the light signal through transduction pathways into the cellular response. Fungi can see and react to a wide range of colors, but most fungi use blue light as their primary signal to regulate its photobiology. Examples of fungal perception of UV, green, and red light, like plants, have been documented and, in most cases, the photoreceptors responsible for these responses have been identified. Blue light is perceived through the activity of light-regulated transcription factors, the WC proteins, first identified in Neurospora crassa. Red light is perceived by phytochromes, a photoreceptor characterized in detail in Aspergillus nidulans. A novel type of rhodopsin, rhodopsin guanylyl cyclase (RGS) has been identified in the zoosporic fungus Blastocladiella emersonii. These types of photoreceptors, together with the blue-light photoreceptor cryptochrome, are widespread in fungi, suggesting that the ancestor of the fungi could see a wide range of colors. Gene duplication and specialization have allowed specific use of fungal photoreceptors in the regulation of fungal biology.

SUMMARYWith varicella-zoster virus (VZV) being a strictly human-specific pathogen, in vitro cell culture models to study the VZV-host cell interactome predominantly rely on the use of primary human cells, immortalized cell lines, and-more recently-stem cell-derived models. In this work, based on literature reports published within the past 15 years, we attempted to summarize major lessons learned from in vitro VZV research, with a specific focus on whether and how a variety of host cells respond upon VZV infection at the cellular level. Following this specific approach, we describe the cellular events occurring following VZV infection in a neural cell type context, an immune cell type context, and a skin cell type context. Highly relevant, and for sure subject to the development of future VZV research, cell types within each of the three compartments reviewed display similarities but also significant differences in cellular response to VZV infection. Clearly, these need further clarification on a cell-type and/or VZV strain-specific level. Finally, to increase physiological relevance, we propose an integrated approach for future VZV-host cell interactome studies on a systems level by using advanced human-induced pluripotent stem cell-derived skin, peripheral, and central nervous system compartments that can be complemented with an isogenic immune cell component. Combined with the implementation of state-of-the-art multi-omics analyses, as well as electrophysiological recordings, this next-generation toolbox for advanced virus-host cell interactome studies may help to elucidate important aspects of VZV biology, including the suggested link between VZV pathology and neurodegenerative diseases.

SUMMARYThe mechanisms by which viruses enter host cells are crucial for their ability to infect and cause disease, serving as major targets for both host immune responses and therapeutic strategies. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry process is primarily driven by the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor, in conjunction with the activity of endosomal cathepsin L and the serine protease transmembrane protease serine 2 (TMPRSS2). Nevertheless, recent scientific advances have expanded our understanding of SARS-CoV-2 entry mechanisms, uncovering alternative receptors and novel cofactors that may enhance viral tropism and adaptability. Given the critical role of the SARS-CoV-2 S protein in mediating host cell entry, it has become a primary target for prevention and therapeutic strategies. However, the continuous spread of SARS-CoV-2 has led to the emergence of S protein variants that may potentially confer a fitness advantage or modify key aspects of SARS-CoV-2 biology, such as transmissibility, infectivity, antigenicity, and/or pathogenicity, posing significant challenges to the efficacy of current interventions. In this review, we provide an updated and comprehensive overview of the latest advances in SARS-CoV-2 entry pathways and molecular mechanisms, exploring their implications for antiviral drug discovery, vaccine design, and the development of other biomedical strategies while addressing the challenges posed by the ongoing evolution of the virus.