mBio最新文献

{"title":"Rethinking the drivers of coronavirus virulence and pathogenesis; toward an understanding of the dynamic world of mutations, indels, and recombination within the alphacoronaviruses.","authors":"Ximena A Olarte-Castillo, Laura E Frazier, Jessica C Gomes Noll, Annette Choi, Gary R Whittaker","doi":"10.1128/mbio.01921-25","DOIUrl":"10.1128/mbio.01921-25","url":null,"abstract":"<p><p>Alphacoronaviruses are widespread but understudied in comparison to betacoronaviruses. Within the alphacoronaviruses is the species <i>Alphacoronavirus-1</i>, which comprises distinct viruses of cats, dogs, and pigs, along with a separate species that infects mustelids-as well as other related viruses of pigs and circulating human viruses. High-pathogenicity feline coronavirus (FCoV) is infamous as the cause of feline infectious peritonitis (FIP), existing as two distinct genotypes (types 1 and 2) and transmitted as a low-pathogenicity virus. The high-pathogenicity variants arise in cats infected with FCoV, and while the mutations responsible remain enigmatic, the main determinant is the spike glycoprotein. FCoV-1 disease outcome is driven by a combination of both within- and between-host evolution. Virulence can be largely explained by the \"internal mutation hypothesis,\" which argues that high-pathogenicity-but poorly transmissible-variants are selected in individual cats. Canine coronaviruses are generally considered low pathogenicity but can cause severe enteritis and can be systemic. Notably, the canine coronavirus spike gene periodically recombines with FCoV-1 to generate FCoV-2, exemplified by FCoV-23, which has caused a widespread outbreak of FIP in Cyprus and has a notably truncated spike N-terminal domain (NTD). In pigs, coronaviruses often cause severe gastrointestinal disease but can become respiratory and have low pathogenicity based on what can also be considered an \"internal deletion\" of the spike NTD. These viruses may exist as a dynamic \"metavirome\" (the sum of all viral genomes present in a sample) that is in a constant state of flux, presenting notable challenges for disease surveillance and management.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0192125"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959250","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":"ASM incorporates Imagetwin to address image duplication and preserve scientific accuracy.","authors":"Aashi P Chaturvedi, Alicea Hibbard, Chad Nelson, Arturo Casadevall, Amy L Kullas","doi":"10.1128/mbio.01990-25","DOIUrl":"10.1128/mbio.01990-25","url":null,"abstract":"<p><p>Image duplication in scientific articles-accidental or intentional-undermines trust in research, authors, institutions, and publishers. Duplications not only cast doubt on researchers' scientific rigor, but they also raise concerns about potential misconduct, jeopardizing careers and even calling into question the effectiveness of the peer review process and editorial oversight. Ultimately, these issues erode confidence in the published study and, more broadly, the entire scientific community. However, when combined with expert in-house staff verification and artificial intelligence-based tools like Imagetwin, Proofig, etc., publishers can detect potential image duplications before publication and strengthen the integrity of the scientific record. In 2023, the American Society for Microbiology (ASM) Journals program integrated Imagetwin into its editorial workflow and conducted a 1-year pilot study. Here, we present key findings and highlight how ASM Journals refined its processes to incorporate image duplication screening earlier in the manuscript lifecycle. The pilot identified image duplications prior to publication in 3.9% of accepted, eligible manuscripts screened with Imagetwin. Most image concerns were unintentional and readily resolved. Of the 2,627 accepted manuscripts screened during the pilot, acceptance was revoked for six (0.23%) due to unresolved issues. It is now a key component of the routine ethics checks performed by ASM journals.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0199025"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959735","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":"Silicon uptake via the transporters SySIT-L and SyLsi-L enhances the growth and photosynthesis of <i>Synechococcus</i> sp. PCC 7002.","authors":"Daixi Liu, Bokun Chen, Yue Meng, Yafei Wang, Wei Zhao, Hongli Ji, Xue Yang, Minghao Zhu, Liwen Zheng, Gang Li, Jihua Liu","doi":"10.1128/mbio.01844-25","DOIUrl":"10.1128/mbio.01844-25","url":null,"abstract":"<p><p><i>Synechococcus,</i> a type of picoplankton, plays a crucial role in the carbon (C) and silicon (Si) biogeochemical cycles of the ocean. Their contribution to biological Si within the oligotrophic oceans can be comparable to that of diatoms. However, the mechanisms of Si assimilation, accumulation, and its impact on cellular metabolism in <i>Synechococcus</i> remain poorly understood. Here, we analyzed the physiological and transcriptomic responses of a model strain <i>Synechococcus</i> sp. PCC 7002 in the exponential growth phase to gradient Si enrichment conditions (0, 25, 50, 120, and 200 μmol L^-1) and performed knockouts of Si transport genes <i>SySIT-L</i> and <i>SyLsi-L</i> to assess relevant function. Results showed that the specific growth rate over 5 days of cultivation was increased by up to 37% in response to Si enrichment under the concentration of 120 μM, accompanied by the physiological parameters, such as cellular content of biological Si and chlorophyll <i>a</i>, as well as elevated rates of photosynthetic O₂ evolution and dark respiration, both of which increased with increasing ambient Si concentration especially on day 1. These changes were corroborated by the transcriptomic analysis. Knockout of the <i>SySIT-L</i> and <i>SyLsi-L</i> genes reduced the cellular Si content by ~80% both on days 1 and 5. Additionally, we found that two Si transporters were widespread in 469 sequenced cyanobacterial genomes. This study provides new scientific evidence from physiological and metabolic perspectives on the role of <i>Synechococcus</i> in the marine Si and C cycles, serving as a valuable starting point for exploring the mechanisms of Si metabolism in picoplankton.IMPORTANCEThis work first reveals the silicon uptake in <i>Synechococcus</i> PCC 7002 via two silicon transporters SIT-L and Lsi-L, which are widely distributed in 469 sequenced cyanobacterial genomes. This enhances photosynthesis and respiration, thus promoting cell growth. Our study serves as a valuable starting point for exploring the mechanisms of silicon metabolism in <i>Synechococcus</i>, providing biological evidence to explain the silicon accumulation of cyanobacteria in the oceans.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0184425"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959577","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":"Distinct modes of cell division drive <i>Anaplasma phagocytophilum</i> morphotype development and the infection cycle.","authors":"Travis J Chiarelli, Savannah E Sanchez, Mary Clark H Lind, Nathaniel S O'Bier, Curtis B Read, Richard T Marconi, Jason A Carlyon","doi":"10.1128/mbio.01972-25","DOIUrl":"10.1128/mbio.01972-25","url":null,"abstract":"<p><p>Pleomorphism is an evolutionary adaptation by which diverse microorganisms maximize their fitness by transitioning between morphologically distinct forms that perform disparate functions in response to the local microenvironment. Cell division is critical for morphotype transition in many pleomorphic bacterial systems. <i>Anaplasma phagocytophilum</i>, which causes the emerging disease granulocytic anaplasmosis, is a pleomorphic obligate intracellular bacterium that lives in a pathogen-modified vacuole except for when it is exocytically released for dissemination to naïve cells. This bacterium cycles between non-infectious, replicative reticulate cell (RC) and infectious, non-replicative dense-cored (DC) forms. Here, we establish that differential modes of <i>A. phagocytophilum</i> cell division drive morphotype development where RC bacteria divide symmetrically to expand the intravacuolar population after which they switch to sacrificial asymmetric division to produce DCs. <i>A. phagocytophilum</i> MreB is crucial for cell division, specifically septation, and thereby formation of both morphotypes. Inhibition of cell division prevents not only DC formation but also <i>A. phagocytophilum</i> vacuole maturation and infectious progeny release, which suggests that these pathogenic processes are coordinated. This study advances understanding of <i>A. phagocytophilum</i> growth and morphotype development and, thus, pathobiology. It also provides the first evidence linking cell division to morphotype development in the <i>Anaplasmataceae</i>.IMPORTANCE<i>Anaplasma phagocytophilum</i>, an obligate intracellular bacterial pathogen that lives in a host cell-derived vacuole, causes human and veterinary diseases of global importance. In the pathogen-occupied vacuole, <i>A. phagocytophilum</i> transitions from a replicative, non-infectious morphotype to a non-replicative, infectious morphotype that is released to spread infection. We established that distinct modes of bacterial cell division drive not only <i>A. phagocytophilum</i> replication but also its differentiation to the infectious form and dissemination to naïve cells. How pleomorphism is regulated in most vacuole-adapted bacterial pathogens is poorly understood. Therefore, this study advances fundamental knowledge of vacuole-adapted pleomorphic bacteria pathobiology and could ultimately identify common novel antibiotic targets for treating the diseases they cause.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0197225"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959766","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":"Experimental system enables studies of <i>Mycobacterium tuberculosis</i> during aerogenic transmission.","authors":"Frank Nuritdinov, Joshua Woo, Markus J Schmidt, Narineh M Odjourian, Melissa Cristaldo, Maureen Dougher, Rosleine Antilus-Sainte, Thomas Heldt, Kyu Rhee, Lydia Bourouiba, Martin Gengenbacher","doi":"10.1128/mbio.00958-25","DOIUrl":"10.1128/mbio.00958-25","url":null,"abstract":"<p><p>Tuberculosis, a persistent public health challenge worldwide, is transmitted when exhaled <i>Mycobacterium tuberculosis</i> (Mtb) particles expelled from an infected individual are inhaled by a susceptible person. To study the adaptation of Mtb during transition between hosts, we developed a transmission simulation system (TSS) that combines controlled pathogen aerosolization and measurement of bioaerosol particle characteristics with in-flight sampling of Mtb and infection of mice by nose-only exposure. Using scattered-light spectrometry, we demonstrated that Mtb aerosol concentrations generated by the TSS better represented human cough than the aerosol concentrations produced by a full-body inhalation exposure system commonly used for Mtb infection of mice. Additionally, the TSS deposited clinically relevant low doses of Mtb into murine lungs with greater precision than the full-body inhalation exposure systems. The TSS revealed a linear correlation between Mtb inoculum concentration and pathogen deposition in murine lungs up to 200 colony-forming units. Higher inoculum concentrations led to a reduction in total particle number, which resulted in disproportionately lower pulmonary infection doses. Importantly, the particle size distributions of Mtb-laden aerosols produced by the TSS mirrored those of tuberculosis patient coughs, with 90% of culturable Mtb found in particles with aerodynamic diameters below 3.3 µm. In conclusion, the TSS represents a novel effective and precise translational platform enabling detailed biophysical and molecular studies of Mtb transmission.</p><p><strong>Importance: </strong>Tuberculosis is transmitted when exhaled <i>Mycobacterium tuberculosis</i> (Mtb)-laden microdroplets of an infected individual are inhaled by a susceptible person. Historically, studies on Mtb transmission have focused mainly on epidemiology due to the technical challenges in replicating the transmission process effectively in a laboratory setting. In this study, we introduce a transmission simulation system (TSS) that integrates controlled Mtb aerosolization, biophysical aerosol particle measurements, in-flight Mtb sampling, and aerosol infection of mice. The TSS generated Mtb bioaerosol concentrations comparable to those produced by human coughs. These pathogen droplets were accurately deposited in mouse lungs at low Mtb doses relevant to human transmission. Notably, the distribution of Mtb among aerosol particles of various sizes closely mirrored that found in the coughs of tuberculosis patients. In summary, the TSS represents a novel tool for conducting molecular studies of Mtb transmission through the air.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0095825"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959787","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":"Genome-wide CRISPRi screen and proteomic profiling identify key genes related to ferulic acid's antifungal activity.","authors":"Ofri Levi, Rina Zuchman, Nour Sleman, Roni Koren, Hazem Khamaisi, Benjamin A Horwitz","doi":"10.1128/mbio.01909-25","DOIUrl":"10.1128/mbio.01909-25","url":null,"abstract":"<p><p>Fungal pathogens of plants must overcome host-imposed stressors, including antimicrobial small molecules. Ferulic acid (FA), a plant-derived phenolic compound, induces fungal stress and cell death. To uncover genetic determinants of FA sensitivity, we performed a genome-wide CRISPR interference (CRISPRi) screen in <i>Saccharomyces cerevisiae</i>. We confirmed that FA impairs yeast growth and triggers stress granule marker sequestration, establishing a relevant selection condition. The CRISPRi screen identified 194 genes involved in the FA-induced stress response and 12 whose repression enhanced resistance. Among them, ERG9, encoding squalene synthase, was most strongly enriched, and its repression conferred FA resistance alongside upregulation of HMG1, implicating the ergosterol biosynthesis pathway. Proteomic profiling of FA-resistant <i>Cochliobolus heterostrophus</i> strains further revealed conserved upregulation of ergosterol biosynthetic enzymes. FA also synergized with fluconazole, a known ergosterol-targeting antifungal, and enhanced susceptibility in azole-resistant <i>Candida albicans</i> strains, suggesting interference with ergosterol metabolism. <i>In planta</i>, FA exhibited dose-dependent antifungal activity, significantly reducing <i>C. heterostrophus</i> lesion formation in maize. These findings establish FA as a promising antifungal agent that targets conserved lipid biosynthesis pathways and overcomes resistance mechanisms, supporting its potential as a sustainable therapeutic and agricultural fungicide.IMPORTANCEFungal infections are a growing threat to human health and agriculture, with rising antifungal resistance limiting treatment options. In this study, we used a genome-wide screening approach to identify ferulic acid (FA), a naturally occurring compound found in plants, as a promising antifungal agent. FA targets the same cellular pathway as many current antifungal drugs and works especially well when combined with fluconazole, a commonly used treatment. Remarkably, FA is also effective against drug-resistant <i>Candida albicans</i> strains, offering hope for new ways to treat difficult infections. In addition to its medical potential, FA protects maize from fungal pathogens, highlighting its usefulness as a sustainable and environmentally friendly crop protectant. These results suggest that FA could be developed into a versatile antifungal agent with applications in both clinical and agricultural settings, helping address the urgent need for new strategies to overcome antifungal resistance.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0190925"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959792","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":"mGem: Revisiting bacterial overflow metabolism.","authors":"Niaz Bahar Chowdhury, Wheaton L Schroeder, Lummy Monteiro, Kristin E Burnum-Johnson","doi":"10.1128/mbio.01193-25","DOIUrl":"10.1128/mbio.01193-25","url":null,"abstract":"<p><p>Bacterial overflow metabolism, where cells perform oxidative fermentation despite the availability of ample oxygen and carbon sources, remains a long-standing paradox in microbial metabolism. Traditional explanations attribute this phenomenon to bacterial physiology, including rapid growth, redox imbalances, competitive advantages in microbiomes, and catabolite repression. However, recent advances in systems biology have revealed additional contributing factors, such as thermodynamic constraints, proteome allocation efficiency, bioenergetics, and the membrane real estate hypothesis. Despite these insights, a comprehensive commentary that critically examines these perspectives is still lacking. In this mGem, we summarize key drivers of overflow metabolism, examine state-of-the-art theories, and identify unresolved questions in current understanding. By evaluating multiple viewpoints, we aim to provide a cohesive analysis of bacterial overflow metabolism and contribute to a broader understanding of microbial physiology, regulatory networks, and evolutionary adaptations shaping metabolic strategies.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0119325"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959877","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":"<i>Gl</i>Slt2 positively regulates <i>Gl</i>Myb-mediated cellulose utilization in <i>Ganoderma lucidum</i>.","authors":"Zi Wang, Yefan Li, Hao Qiu, Zhouyu Li, Tianyu Ji, Ang Ren, Jing Zhu, Liang Shi, Mingwen Zhao, Rui Liu","doi":"10.1128/mbio.01812-25","DOIUrl":"10.1128/mbio.01812-25","url":null,"abstract":"<p><p>Fungal degradation of cellulose facilitates the sustainable harnessing of biosphere energy and carbon cycling. <i>Ganoderma lucidum</i> is one of the basidiomycetes with the largest number of hydrolytic enzymes in its genome. The mycelium of <i>G. lucidum</i> degrades cellulose through the production of substantial amounts of cellulase, enabling the absorption of carbon sources and nutrients essential for fruiting body development. The efficiency with which <i>G. lucidum</i> utilizes cellulose is a determinant of its growth rate. In this study, our findings revealed that the mitogen-activated protein kinase <i>Gl</i>Slt2 positively modulates cellulase activity and cellulose utilization. Furthermore, a yeast two-hybrid (Y2H) screening library found that <i>Gl</i>Slt2 interacts with <i>Gl</i>Myb, an R2R3-type MYB transcription factor. Further studies revealed that <i>Gl</i>Slt2 phosphorylates the S245 site of <i>Gl</i>Myb and that <i>Gl</i>Myb positively regulates cellulose utilization. <i>Gl</i>Myb directly binds to the [A/G] TTAC [G/C] [C/G] motif on the promoters of cellulase-related genes. The S245 site of <i>Gl</i>Myb promotes the binding of <i>Gl</i>Myb to the promoters of cellulase-related genes. Collectively, our findings highlight the mechanism by which <i>Gl</i>Slt2 positively regulates <i>Gl</i>Myb-mediated cellulose utilization. Enhancing cellulose utilization efficiency lays the foundation for the degradation of cellulose in agricultural and forestry waste and facilitates biomass conversion.</p><p><strong>Importance: </strong>The proficient exploitation of cellulose is pivotal for fostering sustainable development, safeguarding the environment, and advancing economic prosperity and technological innovation. Paramount among these benefits is the reduction of reliance on fossil fuels. <i>Ganoderma lucidum</i>, a filamentous fungus, could effectively utilize cellulose from agricultural and forestry waste. Nevertheless, enhancing the efficiency of cellulose utilization from these by-products presents a formidable challenge that demands resolution. In our study, we discovered that GlSlt2 interacts with GlMyb and phosphorylates the S245 site of GlMyb. Further studies have revealed that GlSlt2 positively regulates GlMyb-mediated cellulose utilization. In summary, our findings unveil a sophisticated regulatory mechanism controlling cellulose utilization. These insights lay the foundation for biomass conversion and the biosphere carbon cycle.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0181225"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015729","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":"Reprogramming resistance: phage-antibiotic synergy targets efflux systems in ESKAPEE pathogens.","authors":"Anita Tarasenko, Bhavya N Papudeshi, Susanna R Grigson, Vijini Mallawaarachchi, Abbey L K Hutton, Morgyn S Warner, Jeremy J Barr, Jon Iredell, Bart Eijkelkamp, Robert A Edwards","doi":"10.1128/mbio.01822-25","DOIUrl":"10.1128/mbio.01822-25","url":null,"abstract":"<p><p>Multidrug-resistant (MDR) and extensively drug-resistant (XDR) ESKAPE pathogens pose a significant global health threat due to their ability to evade antibiotics through intrinsic and acquired mechanisms. These bacteria, including <i>Enterococcus faecium</i>, <i>Staphylococcus aureus</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, <i>Escherichia coli,</i> and <i>Enterobacter</i> species, evade antibiotics through intrinsic and adaptive mechanisms. Common strategies include capsule formation, biofilm, β-lactamase production, and efflux activity. Using these mechanisms, bacteria can evade the effects of antibiotics, leading to persistent and difficult-to-treat infections. Understanding the mechanisms of resistance is crucial in developing effective strategies to combat MDR and XDR ESKAPEE pathogens. A promising approach is the development of alternative treatments targeting specific resistance mechanisms in these pathogens. Bacteriophages (phages), which co-evolve with bacterial hosts, offer a dynamic therapeutic alternative by targeting pathogenic bacteria using precision-based strategies. This targeted approach can overcome antibiotic resistance and reduce the risk of damaging the beneficial microbiota. Phages can restore susceptibility in previously untreatable infections by enhancing antibiotic uptake and imposing fitness costs on resistant strains. However, therapeutic deployment faces challenges such as rapid evolution of phage resistance, inconsistent production standards, and limited regulatory pathways. This review examines the mechanistic insights into phage-antibiotic synergy, with a focus on efflux pump-mediated resistance. It discusses emerging therapeutic strategies, current clinical applications, and the translational frameworks needed to integrate phage therapy into mainstream medicine and transform the clinical management of drug-resistant ESKAPEE infections.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0182225"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015749","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":"Evolution and structural diversity of the MotAB stator: insights into the origins of bacterial flagellar motility.","authors":"Caroline Puente-Lelievre, Pietro Ridone, Jordan Douglas, Kaustubh Amritkar, Betül Kaçar, Matthew A B Baker, Nicholas J Matzke","doi":"10.1128/mbio.03824-24","DOIUrl":"10.1128/mbio.03824-24","url":null,"abstract":"<p><p>The rotation of the bacterial flagellum is powered by the MotAB stator complex, which converts ion flux into torque. Despite its central role in flagellar function, the evolutionary origin and structural diversity of this system remain poorly understood. Here, we present the first comprehensive phylogenetic and structural characterization of MotAB and its closest non-flagellar homologs. We gathered homologs from 205 genomes across 27 bacterial phyla, estimated phylogenies, inferred ancestral sequences, and predicted structures for both extant and inferred ancestral proteins using AlphaFold. Our analyses characterized two structurally distinct groups: flagellar ion transporters (FIT) and generic ion transporters (GIT). FIT proteins are structurally conserved, including a characteristic square fold domain and a torque-generating interface (TGI). We further delineate FIT proteins into two subgroups, TGI4 and TGI5s, based on the presence of 4 or 5 short helices within the TGI region. TGI5 motors, such as those found in the <i>Escherichia coli</i> K12 system, are primarily restricted to Pseudomonadota, whereas TGI4 motors, such as the Na⁺-powered polar motors of <i>Vibrio</i> (PomAB), are distributed across a broader range of bacterial lineages. In contrast, GIT proteins exhibit substantial structural and functional heterogeneity and lack features associated with flagellar motility. Nevertheless, a conserved interaction between the A and B subunits is retained across FIT and GIT proteins, with their corresponding genes typically adjacent to operons. Functional assays in <i>E. coli</i> show that FIT-specific structural elements are indispensable for flagellar motility. Our results suggest that the flagellar stator motor complex evolved once from a common ancestral ion transporter, acquiring unique structural traits to support motility. This work provides a robust framework for understanding the evolutionary diversification of stator complexes and their mechanistic specialization.IMPORTANCEFlagellar motility allows bacteria to propel themselves and direct movement according to environmental conditions. It plays a key role in bacterial pathogenicity and survival. We investigated the molecular and structural diversity of the stator motor proteins that provide the ion motive force to power flagellar rotation. This study uses a comparative approach that integrates phylogenetics, 3D protein structure, motility assays, and ancestral state reconstruction (ASR) to provide insights into the structural mechanisms that first powered the flagellar motor. We provide the first phylogenetic and structural characterization and classification of MotAB and relatives.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0382424"},"PeriodicalIF":4.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12505986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030087","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}