Johannes Gibhardt, Michelle M Lieber, Christin S Götz, Frederik Völker, Lars M Blank, Karl Forchhammer, Vijay Jayaraman, Lianet Noda-Garcia, Fabian M Commichau
{"title":"Moonlighting in metabolism: bifunctional enzymes control nitrogen metabolism in <i>Bacillus subtilis</i>.","authors":"Johannes Gibhardt, Michelle M Lieber, Christin S Götz, Frederik Völker, Lars M Blank, Karl Forchhammer, Vijay Jayaraman, Lianet Noda-Garcia, Fabian M Commichau","doi":"10.1128/mmbr.00430-25","DOIUrl":"10.1128/mmbr.00430-25","url":null,"abstract":"<p><p>SUMMARYGlutamate is an essential building block and the most important amino group donor in the cell. The reactions involved in synthesis and degradation link carbon to nitrogen metabolism. The synthesis and activity of the enzymes catalyzing these reactions must, therefore, be precisely regulated. In the Gram-positive model bacterium <i>Bacillus subtilis</i>, glutamate is exclusively synthesized by the combined action of the glutamine synthetase (GS) and the glutamate synthase (GOGAT). The GS catalyzes the ATP-dependent assimilation of ammonium, resulting in the formation of glutamine. Glutamine is converted together with 2-oxoglutarate by the GOGAT into glutamate, which can be used either for further assimilation of ammonium, or as a building block, or amino group donor. The glutamate dehydrogenases (GDHs) GudB and RocG are strictly devoted to glutamate degradation. In recent years, exciting new observations have been made in nitrogen metabolism in <i>B. subtilis</i>. The GS, GOGAT, and the GDHs are multifunctional enzymes, with the GS and GDHs acting as trigger enzymes in the control of gene expression, in addition to their enzymatic activity. The glutamate-synthesizing GOGAT acts as a counter enzyme, inactivating the major GDH GudB to prevent a futile cycle. In this review, we intend to summarize the current state of knowledge about nitrogen metabolism in <i>B. subtilis</i> and discuss open questions that need to be answered in the future.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0043025"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931464","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":"Genetic factors contributing to viral myocarditis.","authors":"Zhihan Wang, Yasir Mohamud, Honglin Luo","doi":"10.1128/mmbr.00357-25","DOIUrl":"10.1128/mmbr.00357-25","url":null,"abstract":"<p><p>SUMMARYViral myocarditis is an inflammatory disease of the heart muscle caused by diverse viral pathogens and shaped by complex interactions between viruses and host responses, ultimately leading to myocardial inflammation and dysfunction. While environmental factors contribute to disease onset, growing evidence highlights a central role for host genetic determinants in influencing susceptibility, severity, and clinical outcomes. In addition, sex-specific differences have emerged as important modifiers of immune responses and disease progression. This review examines the genetic architecture of viral myocarditis, integrating human genetic studies with mechanistic insights derived largely from coxsackievirus B3 (CVB3) models, which provide the most comprehensive experimental framework for dissecting gene-disease relationships <i>in vivo</i>. By integrating genetic associations with their functional implications, we aim to deepen the understanding of viral myocarditis and inform future research directions and potential therapeutic strategies.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0035725"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723087","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}
Katarzyna Potrykus, Katarzyna Bryszkowska, Filip Gąsior, Wiktoria Klasa
{"title":"(p)ppGpp: the magic goes on.","authors":"Katarzyna Potrykus, Katarzyna Bryszkowska, Filip Gąsior, Wiktoria Klasa","doi":"10.1128/mmbr.00413-25","DOIUrl":"10.1128/mmbr.00413-25","url":null,"abstract":"<p><p>SUMMARYBacteria are constantly exposed to changing environmental conditions, and to survive they need to adapt quickly, adjusting their gene expression and metabolism to make the most of the resources available. One of the mechanisms involved is the stringent response, characterized by production of specific guanosine derivatives-ppGpp and pppGpp (collectively called (p)ppGpp). These regulators exert their action and coordinate a global response at many different levels, for example, transcription, translation, nucleotide metabolism, DNA replication, and carbon and lipid metabolism. In this review, we discuss how (p)ppGpp is synthesized and degraded, how it controls different cellular processes and their interplay with other second messengers. A description of differences in (p)ppGpp regulation in Gram-negative and Gram-positive bacteria, along with recent findings and some historical perspectives, is provided. We argue that although much is known about the stringent response and the novel discoveries are definitely advancing the (p)ppGpp field, they are not exhaustive. Instead, they seem to constantly point to aspects that are still waiting to be uncovered-thus, the (p)ppGpp magic goes on.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0041325"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776001","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}
Asha Maria Mathew, Grace Neilsen, Shuiyun Lan, Savannah Leanne Shooter, Jeffrey Shi Jie Zheng, Jeremy Estes, Dongdong Cao, Raymond F Schinazi, Uma S Singh, Bo Liang, Sujin Lee, Stefan G Sarafianos
{"title":"Catching our breath: development of interventions and therapies for respiratory syncytial virus.","authors":"Asha Maria Mathew, Grace Neilsen, Shuiyun Lan, Savannah Leanne Shooter, Jeffrey Shi Jie Zheng, Jeremy Estes, Dongdong Cao, Raymond F Schinazi, Uma S Singh, Bo Liang, Sujin Lee, Stefan G Sarafianos","doi":"10.1128/mmbr.00431-25","DOIUrl":"10.1128/mmbr.00431-25","url":null,"abstract":"<p><p>SUMMARYRespiratory syncytial virus (RSV) continues to be a significant global health concern, particularly affecting infants, young children, and older adults. Although the virus was discovered decades ago, a complete cure remains elusive. RSV is a leading cause of lower respiratory tract infections, contributing to significant illness and mortality around the world. Recent scientific advances have brought promising developments in the fight against RSV. Progress in vaccine technology has led to the approval and distribution of preventative vaccines, particularly for high-risk groups. Monoclonal antibodies, designed to target and neutralize the virus, are used both to prevent and treat infections. Antiviral treatments, though still limited, are also showing potential in reducing disease severity and duration. Advanced animal and controlled human infection models have bolstered preclinical and clinical research, allowing for the testing and refinement of therapeutic candidates in more physiologically relevant systems. These models are playing a crucial role in understanding disease mechanisms and evaluating the efficacy of new interventions. As the field rapidly evolves, it is essential to pause and assess our current standing in the fight against RSV. In many ways, we are finally <i>catching our breath</i>-equipped with better tools and a deeper understanding, yet still facing the challenges of a persistent and complex virus. Continued innovation, investment, and global collaboration will be essential to translate these developments into widespread therapy for those most vulnerable to RSV.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0043125"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13289588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723071","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}
Peter M Allen, Deniz Sinar, Shahar Schwartz, Vayu Hill-Maini
{"title":"Toward synthetic biology in mushroom-forming Agaricomycete fungi: from tools to applications.","authors":"Peter M Allen, Deniz Sinar, Shahar Schwartz, Vayu Hill-Maini","doi":"10.1128/mmbr.00178-25","DOIUrl":"10.1128/mmbr.00178-25","url":null,"abstract":"<p><p>SUMMARYMushroom-forming Agaricomycete fungi underpin global nutrient cycling and carbon sequestration, and support large and growing markets across food, medicinal supplements, and biomaterials. Yet most commercial and research uses still rely on wild-type strains, highlighting the opportunity for genetic engineering to expand possibilities for both fundamental research and biotechnological applications. In this review, we highlight progress toward synthetic biology in Agaricomycetes, and outline the main barriers that limit predictable genetic engineering. We emphasize engineering constraints unique to mushroom biology, including complex sexual cycles, heterokaryosis, and strain instability during transformation and outgrowth. We then transition to gene expression bottlenecks: the scarcity of characterized promoters and terminators, the challenges for gene integration posed by the condensed nature of Agaricomycete genomes, and the effects of introns and specific sequence motifs. Finally, drawing inspiration from progress in related fungi and other eukaryotes, we highlight the priorities for the field: systematic cross-species evaluation of genetic parts, development of more sophisticated gene-editing strategies, higher-throughput screening methods, and the establishment of a unifying model system. These advances would enable new possibilities in the study and use of Agaricomycetes, establishing these elusive organisms as programmable platforms for sustainable biomanufacturing, designer biomaterials, climate solutions, and mechanistic studies of fungal biology.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0017825"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150607","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}
M K Costello, J C McClure, E G Olson, H A Tarcin, H C Mantovani, S C Ricke
{"title":"Looking beyond the rumen: uncovering opportunities to improve health and performance by considering the whole gastrointestinal tract.","authors":"M K Costello, J C McClure, E G Olson, H A Tarcin, H C Mantovani, S C Ricke","doi":"10.1128/mmbr.00057-25","DOIUrl":"10.1128/mmbr.00057-25","url":null,"abstract":"<p><p>SUMMARYModulating the lower gastrointestinal tract (GIT) is an untapped opportunity for improvement in cattle production. The microbial communities across the GIT regions are closely related to host function and anatomical structures, impacting digestion and feed efficiency, the immune response, growth, and methane production. In this review, the characteristics of each GIT location are discussed to better understand how different anatomical structures of the host digestive tract and the microbial communities interact within and between GIT locations. There are several major issues faced by the cattle industry that are impacted by the lower GIT (duodenum, jejunum, ileum, cecum, and large intestines), including managing the inflammatory response, release of waste products, and food safety concerns. As there continues to be a push for agricultural sustainability, improved food safety, reduced economic losses, and efficient early life development, exploring the less understood contributions of the lower GIT is crucial. Finally, this review will explore increasingly convenient and affordable sampling and sequencing techniques that will transform our understanding of the bovine GIT.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0005725"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775964","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}
Jelle Dillen, Laurence T Maeyens, Colin Hill, Sarah Lebeer
{"title":"Updated scheme for the classification of bacteriocins in gram-positive bacteria and a comprehensive overview for Lactobacillaceae.","authors":"Jelle Dillen, Laurence T Maeyens, Colin Hill, Sarah Lebeer","doi":"10.1128/mmbr.00317-25","DOIUrl":"10.1128/mmbr.00317-25","url":null,"abstract":"<p><p>SUMMARYMany gram-positive bacteria, particularly those within the family Lactobacillaceae, possess significant biotechnological potential across food, feed, supplement, pharmaceutical, and agricultural sectors. Numerous species produce bacteriocins or ribosomally synthesized antimicrobial peptides, some of which undergo post-translational modifications that may confer a competitive advantage in complex microbial communities. These beneficial properties, along with their capacity to produce such bioactive molecules, make Lactobacillaceae a valuable microbial group with broad application potential. This review provides a comprehensive overview of bacteriocin classes within Lactobacillaceae, detailing their classification, mechanisms of action, and genetic organization. We propose a unified classification system, including an extension of existing classes and a standardized, source-based nomenclature for ribosomally produced and post-translationally modified peptides (RiPPs) and unmodified bacteriocins from gram-positive bacteria to enhance clarity and consistency. While proposed for Lactobacillaceae, our proposal fits within the broader scope of the field for the development of community standards in line with the scope of, for example, the \"Minimum Information about a Biosynthetic Gene cluster\" (MIBiG) database. We also systematically reviewed all reported bacteriocins within Lactobacillaceae, identifying 474 individual bacteriocins to date. Despite advances in genome and peptidome technologies, most remain only partially characterized. Notably, the majority of producing strains originate from food-related niches, highlighting the untapped potential of species from underexplored environments. Given the growing threat of antibiotic resistance and the demand for natural food preservatives, there is an urgent need to fully characterize these bioactive molecules and discover new ones from lesser-studied Lactobacillaceae species for future applications.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0031725"},"PeriodicalIF":11.8,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776002","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":"Vesicle-driven endomembrane systems in fungi.","authors":"Rebekkah E Pope, Rolf A Prade","doi":"10.1128/mmbr.00297-24","DOIUrl":"10.1128/mmbr.00297-24","url":null,"abstract":"<p><p>SUMMARYIn fungi, the endomembrane system is a pleiomorphic, dynamic network of organelles, driven by vesicle trafficking pathways, which maintain cellular homeostasis, hyphal polar growth, and the secretion of proteins and metabolites. In syncytial hyphae, spatial specialization of organelles and other cellular components of the endomembrane system is evident to support growth and adaptation. Young, apical regions of hyphae contain a Golgi-Spitzenkörper-exocyst triad for rapid polar expansion, whereas distal, older hyphal regions employ unconventional secretion via multivesicular bodies (MVBs), septal vesicle fusion, and extracellular vesicles (EVs) to enhance nutrient acquisition for the entirety of the mycelium. Vesicular trafficking integrates distinct endomembrane compartments into specialized pathways that involve vesicle biogenesis, transport, and fusion to sustain polarized growth and secretion. Actin and microtubules provide tracks for vesicle motility, while Rab GTPases regulate vesicle localization and fusion events. The ESCRT machinery governs MVB formation and scission, COPI/II regulate bidirectional endoplasmic reticulum-Golgi transport, SNARE proteins allow for vesicle and target membrane fusion, and the exocyst complex tethers vesicles to exocytic regions of the plasma membrane. Together, these components form dynamic endomembrane assembly lines that coordinate many cellular processes. The \"distance hypothesis\" predicts that extracellular vesicle-mediated secretion predominates in subapical regions as tip growth slows. This mechanism extends the secretory capabilities of hyphae and promotes broader distribution of secreted enzymes along hyphae. Having a better understanding of spatially regulated secretion pathways will advance our understanding of fungal cell biology and provide strategies to optimize fungi for industrial protein production.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0029724"},"PeriodicalIF":7.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774997","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}
Anuradha Chowdhary, Michail S Lionakis, Neeraj Chauhan
{"title":"<i>Candida auris</i>: host interactions, antifungal drug resistance, and diagnostics.","authors":"Anuradha Chowdhary, Michail S Lionakis, Neeraj Chauhan","doi":"10.1128/mmbr.00187-22","DOIUrl":"10.1128/mmbr.00187-22","url":null,"abstract":"<p><p><b>SUMMARY</b>Invasive 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. <i>Candida auris</i> is a multidrug-resistant fungal pathogen that has a unique ability to grow and persist on human skin. Long-term skin colonization by <i>C. auris</i> is a significant medical concern because colonized patients may facilitate inter- and intra-hospital transmission of <i>C. auris</i> to other patients. Furthermore, <i>C. auris</i>-colonized patients are at risk of developing more serious systemic infections. The diagnosis of <i>C. auris</i> infections is often hampered by misidentification, leading to delays in starting appropriate antifungal therapy. Here, we summarize the global burden of candidiasis due to <i>C. auris</i>, 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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0018722"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668890","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":"Mutation-based mechanisms of antibiotic resistance.","authors":"Rajeev Misra","doi":"10.1128/mmbr.00101-25","DOIUrl":"10.1128/mmbr.00101-25","url":null,"abstract":"<p><p>SUMMARYAntibiotic resistance is a major global health threat, with an estimated 1.14 million deaths in 2021 linked to antibiotic resistance. Mutations naturally arise as bacteria evolve to defend against and survive various environmental challenges, including those exerted by antibiotics. Both overuse and misuse of antibiotics can accelerate selection for resistant bacteria. Misuse can happen when antibiotic treatment ends prematurely, resulting in sub-lethal antibiotic levels. This provides an ideal environment for the proliferation of resistance-causing mutations, which, in some cases, are enhanced further by triggering the synthesis of error-prone DNA polymerases. Low levels of antibiotics are also found in the environment, creating breeding grounds for the evolution of antibiotic resistance. Mutations diminish the impact of antibiotics by three principal mechanisms: (i) reducing antibiotic influx, (ii) elevating antibiotic efflux, and (iii) altering cellular targets of antibiotics. The first two mechanisms confer modest resistance against a broad range of antibiotics; however, in combination with the third target-specific mechanism, they become the foundation of high-level antibiotic resistance. Ultimately, while the manifestation of mutations cannot be prevented, steps can be taken to lower their frequency by carefully considering the need for antibiotic prescription, exploring combination therapies, integrating adjuvants such as efflux pump inhibitors, and minimizing environmental contamination of antibiotics.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0010125"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113727","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}