{"title":"Gene regulation in <i>Bacteroides fragilis</i>: adaptive control in a dynamic host environment.","authors":"Daniel Ryan","doi":"10.1128/mmbr.00225-25","DOIUrl":"https://doi.org/10.1128/mmbr.00225-25","url":null,"abstract":"<p><p><b>SUMMARY</b><i>Bacteroides fragilis</i> occupies a dynamic position within the human gut. Though it comprises a relatively minor fraction of the gut microbiota, it is disproportionately enriched at extraintestinal sites of infection. This ability to survive in contrasting host environments pivots on a regulatory framework that is both modular and highly plastic. Rather than deploying a suite of hierarchical global regulators, <i>B. fragilis</i> employs numerous operon-embedded transcriptional switches, including site-specific DNA inversions, phase-variable epigenetic systems, extracytoplasmic function sigma/anti-sigma factor pairs, and hybrid two-component systems. These networks are further complemented by cis-regulatory elongation checkpoints and post-transcriptional control by small RNAs. This review explores the full spectrum of these regulatory mechanisms, highlighting how they facilitate niche adaptation, surface variation, immune evasion, and metabolic prioritization. It also explores intraspecies variation focusing on glycan metabolism, antibiotic resistance, and virulence. Additionally, it outlines recombination-driven regulation, alongside extracytoplasmic function sigma factor diversification, flexible promoter architecture, and elongation checkpoints, each contributing to the evolution of transcriptional control in <i>B. fragilis</i>. Finally, it outlines unanswered questions, including the largely unexplored sRNA regulon, the coordination of DNA inversions, elongation control, and phase-variable methylation, and proposes experimental strategies to investigate the integration of these regulatory systems during environmental transitions. Taken together, <i>B. fragilis</i> emerges as a model bacterium for studying decentralized gene regulation in complex microbial ecosystems, with implications for both microbial ecology and therapeutic targeting of the gut microbiota.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0022525"},"PeriodicalIF":7.8,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Tishchenko, Fien Van Raemdonck, Herman W Favoreel
{"title":"Deceiving the gatekeepers: virus modulation of gap junctions.","authors":"Alexander Tishchenko, Fien Van Raemdonck, Herman W Favoreel","doi":"10.1128/mmbr.00091-25","DOIUrl":"https://doi.org/10.1128/mmbr.00091-25","url":null,"abstract":"<p><p>SUMMARYGap junctions (GJs) are specialized intercellular channels that mediate the direct exchange of ions, metabolites, and signaling molecules between adjacent cells, playing essential roles in tissue homeostasis and immune coordination. Their function is tightly controlled by connexin isoform composition, trafficking and turnover, and post-translational modifications, particularly phosphorylation and ubiquitination. This review synthesizes current knowledge on the diverse strategies employed by DNA and RNA viruses, including members of the <i>Herpesviridae</i>, <i>Adenoviridae, Papillomaviridae</i>, <i>Polyomaviridae</i>, <i>Retroviridae</i>, <i>Flaviviridae</i>, <i>Coronaviridae, Orthomyxoviridae, Bornaviridae, Peribunyaviridae,</i> and <i>Picornaviridae</i> families, to modulate gap junctional intercellular communication (GJIC) and the constituent connexin proteins. We highlight mechanisms such as phosphorylation-induced GJ closure and degradation, subcellular mislocalization, and transcriptional and post-transcriptional regulation of connexin expression. Viral modulation of GJIC serves a variety of purposes, including promoting viral spread, suppressing innate immune responses mediated by the cGAMP/STING pathway, and facilitating oncogenic transformation. Downregulation and/or selective reprogramming of GJIC during viral transformation mirrors changes seen in non-viral cancers, indicating that GJIC manipulation represents a shared mechanism underpinning both viral and non-viral cellular transformation in solid tumors. By integrating findings across diverse virus families, this review underscores GJIC modulation as a central virus-host interaction axis and identifies potential therapeutic targets for modulating GJIC in viral infections.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0009125"},"PeriodicalIF":7.8,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145292752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HIV reservoirs in lymphomagenesis: hidden driver in the era of viral suppression?","authors":"Yaoguang Li, Qing Xiao, Fengting Yu, Fujie Zhang","doi":"10.1128/mmbr.00104-25","DOIUrl":"https://doi.org/10.1128/mmbr.00104-25","url":null,"abstract":"<p><p>SUMMARYDespite advancements in antiretroviral therapy, people living with HIV (PLWH) remain at high risk of lymphoma. The persistence of HIV reservoirs and their spatial association with lymphoma highlights the need to clarify their role in lymphomagenesis. HIV reservoirs, which are established early during infection and maintained through clonal expansion, epigenetic silencing, and immune evasion, may contribute to lymphomagenesis through four interconnected mechanisms: provirus integration effects, viral protein-mediated disturbances, microenvironment dysregulation, and reservoir reactivation. Current therapeutic approaches that simultaneously target HIV reservoirs and lymphoma-including allogeneic hematopoietic stem cell transplantation, chimeric antigen receptor T-cell therapy, and immune checkpoint inhibitors-show promise but face substantial challenges. There is an urgent need to develop accessible strategies that can both eradicate HIV reservoirs and mitigate lymphoma risk. Such efforts may ultimately enable a \"double cure\" for PLWH with lymphoma, offering new hope against this life-threatening comorbidity. This review summarizes the potential links between HIV reservoirs and HIV-associated lymphoma and outlines emerging therapeutic avenues toward achieving a double cure.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0010425"},"PeriodicalIF":7.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dmitri V Mavrodi, Wulf Blankenfeldt, Olga V Mavrodi, David M Weller, Linda S Thomashow
{"title":"Microbial phenazines: biosynthesis, structural diversity, evolution, regulation, and biological significance.","authors":"Dmitri V Mavrodi, Wulf Blankenfeldt, Olga V Mavrodi, David M Weller, Linda S Thomashow","doi":"10.1128/mmbr.00147-23","DOIUrl":"https://doi.org/10.1128/mmbr.00147-23","url":null,"abstract":"<p><p>SUMMARYPhenazines are small, redox-active secondary metabolites produced by various bacterial species. These compounds participate in electron-transfer reactions, aiding microbes in surviving stressful or oxygen-limited environments. In this review, we examine the extensive structural diversity of phenazines and trace the evolutionary history of their biosynthetic pathways, which often move between distantly related species through horizontal gene transfer. We also explore how environmental factors such as nutrient levels and cell-to-cell signaling regulate phenazine production. Beyond their roles in microbial physiology, phenazines influence interactions among organisms, acting as antimicrobial agents, signaling molecules, and factors that shape microbiome dynamics in soils, plant roots, and other habitats. A better understanding of phenazine biology reveals how microbes adapt and thrive in diverse environments and emphasizes the potential applications of these compounds in agriculture and human health.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0014723"},"PeriodicalIF":7.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chengjun Cao, Li Tao, Tianren Hu, Haiqing Chu, Austin M Perry, Clarissa J Nobile, Guanghua Huang
{"title":"Genetic and environmental control of parasexual reproduction in the pathogenic <i>Candida</i> species.","authors":"Chengjun Cao, Li Tao, Tianren Hu, Haiqing Chu, Austin M Perry, Clarissa J Nobile, Guanghua Huang","doi":"10.1128/mmbr.00002-25","DOIUrl":"https://doi.org/10.1128/mmbr.00002-25","url":null,"abstract":"<p><p>SUMMARY<i>Candida</i> species are major yeast pathogens that cause both mucosal candidiasis and life-threatening invasive infections. Most <i>Candida</i> species, including <i>Candida albicans</i>, have long been thought to be \"imperfect\" due to the lack of a complete sexual reproduction cycle. Since the discovery of the mating type-like locus in <i>C. albicans</i> in 1999, the regulation of (para)sexual reproduction has been intensively investigated in this organism as well as in several phylogenetically closely related species. The (para)sexual cycle is not only critical for the generation of genetic and phenotypic diversity but is also involved in the regulation of other biological processes, such as morphological transitions, biofilm development, and virulence in pathogenic fungi. In this review article, we focus on the unique characteristics and genetic and environmental regulatory mechanisms of parasexual reproduction in the pathogenic <i>Candida</i> species. We discuss the relationship between the white-opaque switching and mating in the <i>Candida</i> species, particularly in <i>C. albicans</i>. We describe recent findings on environmental factors, genetic regulators, and key signaling pathways involved in sexual mating in <i>C. albicans</i> and related species. Finally, we discuss the mating potential and associated regulatory machinery in several <i>Candida</i> species, where parasexual reproduction has not been observed and bring to light some open-ended questions regarding the unique features of parasexual reproduction that should be addressed in future studies in the field.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0000225"},"PeriodicalIF":7.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peptidoglycan polymerase function and regulation.","authors":"Mohammed Terrak, Frédéric Kerff","doi":"10.1128/mmbr.00070-25","DOIUrl":"10.1128/mmbr.00070-25","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0007025"},"PeriodicalIF":7.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susanna R Grigson, George Bouras, Bas E Dutilh, Robert D Olson, Robert A Edwards
{"title":"Computational function prediction of bacteria and phage proteins.","authors":"Susanna R Grigson, George Bouras, Bas E Dutilh, Robert D Olson, Robert A Edwards","doi":"10.1128/mmbr.00022-25","DOIUrl":"10.1128/mmbr.00022-25","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0002225"},"PeriodicalIF":7.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana E Juarez, Alejandra Krüger, Paula M A Lucchesi
{"title":"Shiga toxin-producing <i>Escherichia coli</i>, food contamination, and bacteriophages as a control strategy.","authors":"Ana E Juarez, Alejandra Krüger, Paula M A Lucchesi","doi":"10.1128/mmbr.00244-25","DOIUrl":"10.1128/mmbr.00244-25","url":null,"abstract":"<p><p>SUMMARYShiga toxin-producing <i>Escherichia coli</i> (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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0024425"},"PeriodicalIF":7.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144960805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polio virotherapy provokes MDA5 signaling and CD4<sup>+</sup> T cell help to mediate cancer <i>in situ</i> vaccination.","authors":"Matthias Gromeier, Michael C Brown","doi":"10.1128/mmbr.00040-24","DOIUrl":"10.1128/mmbr.00040-24","url":null,"abstract":"<p><p>SUMMARYThere is overwhelming evidence that antitumor CD8<sup>+</sup> T cell responses can mediate effective tumor control. CD8<sup>+</sup> 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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0004024"},"PeriodicalIF":7.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unraveling the complexities of neurotropic virus infection and immune evasion.","authors":"Abhishek Kumar Verma, Stanley Perlman","doi":"10.1128/mmbr.00185-23","DOIUrl":"10.1128/mmbr.00185-23","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0018523"},"PeriodicalIF":7.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}