Microbiology and Molecular Biology Reviews最新文献

{"title":"Overcoming the energy-dependent barrier to aminoglycoside uptake: multimodal strategies to sensitize <i>Staphylococcus aureus</i> persisters.","authors":"Seongeun Baek, Young June Choe, Philip S Yune, Eleftherios Mylonakis, Wooseong Kim","doi":"10.1128/mmbr.00440-25","DOIUrl":"10.1128/mmbr.00440-25","url":null,"abstract":"<p><p>SUMMARYPersistent <i>Staphylococcus aureus</i> infections pose a major therapeutic challenge due to the formation of metabolically dormant persister cells that survive antibiotic exposure without acquiring genetic resistance. Despite their potent bactericidal activity, aminoglycosides fail against these persisters due to their reliance on energy-dependent uptake driven by the proton motive force (PMF). This review synthesizes emerging strategies designed to overcome this critical bottleneck. Metabolic stimulation using specific carbon sources or PMF-modulating agents reactivates membrane energetics, thereby restoring aminoglycoside uptake in dormant cells. Membrane-targeting adjuvants bypass PMF altogether, enabling antibiotic entry via biophysical remodeling and disruption of the lipid bilayer. Additionally, we discuss rationally engineered aminoglycoside hybrids, such as peptide-conjugated variants, that achieve self-directed, energy-independent penetration while preserving ribosomal targeting. Collectively, these approaches highlight that aminoglycoside failure against <i>S. aureus</i> persisters can be a modifiable physiological limitation rather than an issue of intrinsic resistance. The convergence of metabolic and membrane-based potentiation underscores the therapeutic potential of combinatorial regimens tailored to the unique bioenergetic state of persisters. Their clinical translation, combined with efforts to address toxicity, may transform the treatment landscape of recalcitrant <i>S. aureus</i> infections and mitigate the risk of relapse.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0044025"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258670","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":"Beyond stool: sampling context and inferential scope in gut mechanistic studies.","authors":"Rebecca Lewandowski","doi":"10.1128/mmbr.00212-26","DOIUrl":"10.1128/mmbr.00212-26","url":null,"abstract":"<p><p>SUMMARYHuman gut microbiome research still relies heavily on fecal sampling because stool is noninvasive, scalable, repeatable, and essential for population-level and longitudinal studies. These strengths have made stool central to human microbiome science, but fecal output is not a neutral representation of every intestinal compartment. It reflects material that has persisted through digestion, transport, microbial turnover, host absorption, and distal colonic processing. This distinction becomes important when studies move from detecting microbial associations to explaining localized activity, host-interface interaction, inducible viral states, metabolic flux, or clinical consequences. This review proposes a framework for aligning sampling context with inferential scope across five evidence domains. These include distal output detection, regional luminal measurement, host-interface measurement, linked functional response, and patient-level consequence. The framework is not intended to rank specimen types or require every study to escalate toward invasive sampling. Instead, it clarifies which claims are supported by stool, luminal sampling, mucosal or host-proximal measurements, experimental models, and clinical metadata when used alone or in combination. Prophage induction and fecal short-chain fatty acid measurements are used as examples of a broader methodological issue. Detection in feces can be highly informative, but it does not by itself localize activity, establish mechanism, or demonstrate host consequence. As gut microbiome research increasingly seeks mechanistic explanations, sampling strategy should be treated as part of inference itself.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0021226"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794592","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":"From dividing to dormant: embracing the full activity spectrum for environmental microorganisms.","authors":"Ludivine Guigard, Victor Bal, A Fina Bintarti, Margaux Buron, Emma Chavan, Milena Gonzalo, Xipeng Liu, Wei Zheng, Ashley Shade","doi":"10.1128/mmbr.00354-25","DOIUrl":"10.1128/mmbr.00354-25","url":null,"abstract":"<p><p>SUMMARYMicroorganisms can cope with stress by entering dormancy, a viable state of reduced metabolic activity that enables persistence, dispersal, and long-term survival. However, microbial life in environmental systems is best understood as a spectrum of metabolic activity, spanning from highly active, dividing cells to deeply dormant phenotypes. This spectrum reflects dynamic survival strategies under fluctuating conditions, with critical implications for ecosystem stability, gene dissemination, and resilience to disturbances in natural and human-influenced systems. Yet, microbial activity is often treated as binary (active vs. dormant), oversimplifying a biological continuity that remains technically difficult to quantify. Here, we synthesize advances in microbial dormancy to reconceptualize activity as a spectrum. We review current and emerging methods to quantify environmental activity, linking each to the Central Dogma of molecular biology (DNA to RNA to protein) to guide interpretation along a generalizable continuum. Through a literature synthesis of terrestrial, aquatic, and wastewater treatment ecosystems, we compare how methods estimate active cells and populations. We recommend standardized reporting of total community size, active cell abundance, and proportional activity to enrich the interpretation of microbiome 'omics data, with activity intensity and active-inactive switching providing deeper insights. To achieve this, we advocate for increased accessibility and throughput of precise activity-discriminating technologies, alongside renewed use of reliable methods like direct cell counts and activity stains. Adopting this spectrum-based perspective will improve our ability to tackle key societal challenges, such as understanding microbial contributions to ecosystem function under climate change and gene dispersal at human-environment interfaces.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0035425"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148318191","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":"To lyse or not to lyse: biasing bacteriophage behaviors.","authors":"Rabia Fatima, Gayatri Nair, Amany Al-Anany, Alexander P Hynes","doi":"10.1128/mmbr.00254-25","DOIUrl":"10.1128/mmbr.00254-25","url":null,"abstract":"<p><p>SUMMARYHow temperate bacteriophages choose between lysis and lysogeny (dormancy) was one of the very first-and remains among the best studied-models of gene regulation. As over 75% of bacteria have a dormant phage within their genomes, the impact of this decision is far-reaching. It is also underappreciated, with much of microbiology studied independently of this decision; for example, the ubiquitous lab <i>E. coli</i> strain K-12 was cured of phage lambda to make it a \"better\" model. Here, we review why phages \"choose\" to lyse or not to lyse, the wide variety of signals they can respond to, how these signals are tapped into by the phage, how the timing of the decision impacts its outcome, and how phages interact around this decision. This decision underpins so much of bacteriology that an understanding of it, and the resulting ability to bias it, will help explain phenomena ranging from failures in culturing bacteria to successes of antibiotic treatments.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0025425"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669976","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":"Falling asleep: the importance of ribosome hibernation in bacteria.","authors":"Robert Karari Njenga, Hans-Georg Koch","doi":"10.1128/mmbr.00159-25","DOIUrl":"10.1128/mmbr.00159-25","url":null,"abstract":"<p><p>SUMMARYThe biogenesis of ribosomes and protein synthesis are among the most energy-consuming processes in living cells and therefore rate-limiting for growth, making them key targets for controlling the growth of competitors, predators, and pathogens. Cells also restrict their own protein synthesis under nutrient limitation or other stress conditions. A universally conserved strategy involves ribosome hibernation, in which specialized factors reversibly silence ribosomes. This protects ribosomes from being degraded by RNases and proteases, and at the same time allows for their fast reactivation when conditions improve. In bacteria, multiple hibernation factors act in parallel through distinct mechanisms. Well-characterized factors, such as ribosome modulation factor (RMF) and hibernation-promoting factor (HPF) and its homologs, block the mRNA channel and occupy the A- and P-sites of the small ribosomal subunit. Other factors, such as ribosome silencing factor S (RsfS), prevent the association of the 30S ribosomal subunit with the 50S subunit. Recently characterized factors include the paralogous C-tail-anchored membrane proteins YqjD, ElaB, and YgaM, which inactivate ribosomes by blocking the peptide exit tunnel. The coordinated production of these factors is tightly linked to broader stress response pathways, ensuring that ribosomal activity is modulated in accordance with cellular needs. In this review, we describe the diverse mechanisms that bacteria such as <i>E. coli</i> use to silence ribosomes and highlight the flexibility and significance of ribosome hibernation as a conserved strategy for saving energy and for cellular adaptation to stress conditions.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0015925"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148620178","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":"Lifestyle plasticity and the shared hypocrealean toolkit across <i>Fusarium</i>, <i>Metarhizium</i>, and <i>Trichoderma</i>.","authors":"Raymond J St Leger, Huiyu Sheng, Alexander X Hafer","doi":"10.1128/mmbr.00116-25","DOIUrl":"10.1128/mmbr.00116-25","url":null,"abstract":"<p><p>SUMMARYFungi in the genera <i>Fusarium</i>, <i>Metarhizium</i>, and <i>Trichoderma</i> (FMT) are traditionally defined by their roles as plant pathogens, insect pathogens, and mycoparasites, respectively. However, these classifications obscure both their shared hypocrealean ancestry and the remarkable ecological plasticity that characterizes all three genera. Across these lineages, plant endophytism appears to represent the predominant ecological state, with frequent transitions among saprotrophy, symbiosis, pathogenicity, and antagonism. Comparative genomics reveals that FMT fungi possess two-speed genomes comprising conserved core chromosomes and dynamic accessory regions enriched in host-interaction and secondary metabolism genes. These architectures support a shared hypocrealean genomic toolkit that has been differentially modified across lineages. In <i>Fusarium</i>, transitions along the mutualism-to-pathogenicity continuum appear to be driven primarily by regulatory plasticity rather than by major changes in gene content. By contrast, <i>Metarhizium</i> and <i>Trichoderma</i> expanded from ancestral pathogenic states toward broader plant associations through horizontal gene transfer, gene duplication, and diversification of host-recognition, signaling, and metabolite-production pathways. Reproductive strategies similarly reflect ecological divergence. Generalist lineages are predominantly clonal, whereas specialists more frequently retain sexual reproduction, facilitating adaptation to predictable hosts and environments. Ecologically, FMT fungi occupy overlapping but distinct niches: <i>Trichoderma</i> dominates stable environments through mycoparasitism and competitive exclusion; <i>Fusarium</i> thrives in disturbed habitats through rapid colonization of stressed plants; and <i>Metarhizium</i> bridges soil, plant, and insect environments through combined root association and insect pathogenicity. Collectively, FMT fungi illustrate how divergent ecological strategies can emerge through differential modification and regulatory deployment of a shared hypocrealean genomic toolkit.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0011625"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549479","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":"Chemo-selective proteomics in microbial systems.","authors":"Grace Z Wang, Chelsey M VanDrisse","doi":"10.1128/mmbr.00099-26","DOIUrl":"https://doi.org/10.1128/mmbr.00099-26","url":null,"abstract":"<p><p><b>SUMMARY</b>Over the past two decades, the field of bioorthogonal chemistry has transitioned from emerging to an established cornerstone of scientific inquiry. In parallel, advances in microbial and host-microbe research have highlighted the need for functional approaches that extend beyond genomic and transcriptomic analyses to directly interrogate protein-level activity. Despite this need, proteomic strategies capable of resolving dynamic, heterogeneous, and low-abundance protein populations remain underdeveloped in microbial systems. This review highlights the convergence of chemo-selective proteomic technologies with microbial biology, focusing on <u>b</u>io<u>o</u>rthogonal <u>n</u>on-<u>c</u>anonical <u>a</u>mino acid <u>t</u>agging (BONCAT), activity- or affinity-based protein profiling, and bioorthogonal post-translational modifications, and comments on possibilities for novel applications for the use of click chemistry-based tools in the functional interrogation of microbial systems. Together, these strategies enable spatiotemporal resolution of protein synthesis, selective profiling of microbial subpopulations, and direct characterization of protein activity and regulation in complex biological contexts, including single-species cultures, host-associated environments, and polymicrobial communities. Continued development and utilization of these technologies will enable deeper mechanistic insight into how microbial systems function and respond to environmental and host-derived cues.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0009926"},"PeriodicalIF":11.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969980","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":"From confrontation to co-adaptation: the dynamic dialogue of <i>Candida albicans</i> and macrophages.","authors":"Pedro Miramón, Hannah B Wilson, Michael C Lorenz","doi":"10.1128/mmbr.00191-22","DOIUrl":"https://doi.org/10.1128/mmbr.00191-22","url":null,"abstract":"<p><p>SUMMARY<i>Candida</i> is a taxonomically fluid genus that includes several opportunistic pathogens, for which the clinical incidence has been increasing for decades. Though <i>Candida</i> now represents a lower proportion of cases than in the past, <i>Candida albicans</i> remains the most prevalent species in human infections, and disseminated candidiasis remains associated with an unacceptably high mortality rate in immunocompromised patients. Most individuals are protected by the innate immune system, of which phagocytes are a key mediator. The complex dynamic between <i>C. albicans</i> and macrophages has become an important model system for host-pathogen interactions in which both sides engage in intricate developmental programs to respond to the other. In this review, we discuss the molecular mechanisms of recognition and response with a focus on <i>C. albicans</i>, but including other <i>Candida</i> species, with an eye toward therapeutic interventions to improve patient outcomes.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0019122"},"PeriodicalIF":11.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963557","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":"Phytohormones in fungi: inter-kingdom modulators or fungal self-controlling elements?","authors":"David A García-Estrada, Melanie Ruvalcaba-Villagrán, Axel G Sánchez-Fonseca, Jonathan Duran-Palmerin, Juan Ornelas-Paz, Francisco Vargas-Gasca, Vianey Olmedo-Monfil, Alfredo Herrera-Estrella","doi":"10.1128/mmbr.00261-25","DOIUrl":"https://doi.org/10.1128/mmbr.00261-25","url":null,"abstract":"<p><p>SUMMARYLeveraging data from innovative experimental approaches, omics technologies, and bioinformatics, we offer new insights into how fungi communicate with and perceive their environment to achieve ecological success. By integrating comparative data from both the fungal and plant kingdoms, we critically reassessed the evolutionary, biochemical, and functional landscape of phytohormones in fungi, challenging the conventional notion that these molecules serve exclusively as plant regulators or as means of communication with them. Our analysis demonstrates that fungi not only synthesize a diverse array of phytohormones-including auxins, cytokinins, gibberellins, abscisic acid, ethylene, brassinosteroids, salicylic acid, and oxylipins-but also possess hormone-sensing and signal transduction mechanisms architecturally distinct from those of plants. Employing genomics, phylogenetics, and structural analyses, the review uncovers that many hormone biosynthetic and sensing pathways in fungi are evolutionarily ancient, sometimes predating their roles in plant-fungus interactions, and that some pathways show convergence rather than direct gene homology. Fungal phytohormones regulate development, growth, and metabolism, thereby playing key functions in their ecological context. The review emphasizes that, while biosynthetic pathways tend to be highly conserved, perception and signaling mechanisms in fungi are more varied and often remain poorly understood. We conclude that fungi have an intrinsic and autonomous hormonal physiology that underpins their ecological adaptability and success. Collectively, this analysis reframes fungal biology, highlighting the need for deeper investigation into the signaling and regulatory roles of phytohormones in fungi beyond their interactions with plants.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0026125"},"PeriodicalIF":11.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963482","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":"LD-transpeptidation in bacterial cell walls: biochemical principles and functional diversity.","authors":"Barbara Walenkiewicz, Laura Alvarez, Felipe Cava","doi":"10.1128/mmbr.00090-24","DOIUrl":"10.1128/mmbr.00090-24","url":null,"abstract":"<p><p>SUMMARYPeptidoglycan (PG) is a dynamic, load-bearing polymer whose crosslinking chemistry governs envelope mechanics, growth modes, and stress tolerance. For decades, PG crosslinking was viewed primarily through the lens of penicillin-binding proteins (PBPs). However, accumulating evidence over the past 2 decades has established LD-transpeptidases (LDTs) as important contributors to PG remodeling. Here, we organize the expanding LDT field into macro-domains bridging biochemistry, evolution, and ecology. We initially describe the reaction mechanisms, structural diversification, and convergent solutions and then explore the evolution across species. We highlight non-canonical LD-crosslinking chemistries, including L-Ala-<i>meso</i>-DAP (1-3) linkages, that broaden the design space of the sacculus. We then map functional repertoires across lineages-from reinforcement during envelope stress to outer membrane tethering, predation, specialized secretion, dormancy, and biofilms. In pathogens where LD-crosslinking is dominant or essential, carbapenems and penems remain particularly effective inhibitors of LDTs, yet family-wide diversity calls for structure-guided selectivity and ecological awareness. We also chart underexplored connections to microbiome ecology and propose LDT-derived biomarkers that report growth modes and dormancy. We integrate dispersed evidence into a complete landscape in which two-component systems and environmental cues coordinate LD pathways. Building on these threads, we propose a unifying model of LDTs as adaptive architects of PG whose acyl-enzyme intermediate and modular substrate gating endow reversibility, partner choice, and context-dependent outcomes-reinforcement, remodeling, anchoring, or controlled self-breach. Finally, we outline methods that enabled the discovery of LDTs and explore future directions. Together, these perspectives reframe LDTs from auxiliary enzymes to central designers of envelope architecture and bacterial fitness.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0009024"},"PeriodicalIF":11.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430677","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}