mBio最新文献

{"title":"A bundled anti-parallel cytochrome nanowire structure suggests roles in cell-cell electron transfer and biofilm formation.","authors":"Holly A Petersen, Chi H Chan, Gilbert O Carpenter, Media Zakizadeh Tabari, Jessie Lynda Fields, Ayisha Zia, Shane T Rich-New, Allon I Hochbaum, Daniel R Bond, Fengbin Wang","doi":"10.1128/mbio.00906-26","DOIUrl":"10.1128/mbio.00906-26","url":null,"abstract":"<p><p>Long-range extracellular electron transfer enables respiring microbes to use minerals, organisms, or electrodes as electron acceptors by transporting electrons microns away from the cell surface. This process is primarily studied in <i>Geobacter sulfurreducens</i>, which produces at least three distinct, micrometer-long, multiheme cytochrome nanowires capable of electron transfer. However, the distribution and higher-order structure of such nanowires remains largely unknown. Here, we employed cryo-electron microscopy to determine the atomic structure of a unique cytochrome nanowire from <i>Desulfuromonas soudanensis</i> WTL, a halophilic, iron- and electrode-reducing bacterium from deep subsurface brine. These filaments are based on an OmcE tetraheme cytochrome homolog that assembles into highly ordered bundles of anti-parallel filaments. Electronic measurements of purified nanowire bundle films reveal that these bundles are conductive, with conductance increasing in a concentration-dependent manner. The apparent midpoint potential of these OmcE bundles was -145 mV vs SHE. They exhibit redox activity over a ~370 mV window attributable to five electrostatically coupled hemes, suggesting heme-heme interaction beyond the boundaries of individual OmcE repeat units. Observations of these bundles under diverse buffer conditions suggest that they represent stable supramolecular assemblies, although direct <i>in vivo</i> confirmation within intact biofilms remains a future goal. Furthermore, a similar cytochrome bundle structure was observed in <i>Geobacter metallireducens</i>, showing that this quaternary structure may be a common feature among nanowires secreted by electroactive microbes. Our findings demonstrate that cytochrome nanowires are widespread and can form specialized bundle interfaces. This novel state could facilitate conductive biofilm formation and form the basis for direct microbial electron exchange.<b>IMPORTANCE</b>All available structures of filaments containing a central core of closely spaced multiheme c-type cytochromes are derived from only a few organisms and are based on individual fibers easily imaged by cryo-electron microscopy. While imaging enriched preparations of extracellular appendages from a bacterium isolated from deep subsurface brine, we observed ordered bundles of anti-parallel cytochrome filaments. This quaternary arrangement contained specific contacts between adjacent nanowires, and a similar structure could be found in a relative from a related genus. This first report of bundling by nanowires suggests that such conductive structures may be missed in traditional surveys searching for novel filaments and provides an explanation for how nanowires could directly link adjacent cells in biofilms and granular communities.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0090626"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819089","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":"Growth-dependent tRNA reprogramming and codon bias link translation to metabolic state in <i>Enterococcus faecalis</i>.","authors":"Michelle M Mitchener, Caleb M Anderson, Mark Veleba, Kayla Teo, Mélanie Roch, Ruixi Chen, Yifeng Yuan, Isaiah Han, Agnieszka Dziergowska, Kevin Pethe, Thomas J Begley, Kimberly A Kline, Peter C Dedon","doi":"10.1128/mbio.01474-26","DOIUrl":"10.1128/mbio.01474-26","url":null,"abstract":"<p><p><i>Enterococcus faecalis</i> is a gram-positive commensal bacterium of the human gut microbiome and an opportunistic pathogen responsible for many hospital-acquired infections. Despite the clinical importance of <i>E. faecalis</i>, how gene and protein expression are coordinated with growth remains poorly defined. Here, we profiled transcript, protein, and tRNA pool dynamics across distinct phases of <i>E. faecalis</i> growth. Differences in protein abundance and corresponding mRNA levels suggested growth phase-dependent posttranscriptional regulation. Growth-associated genes exhibited biased synonymous codon usage, with ribosomal and glycolytic proteins enriched in low-abundance codons read by queuosine-modifiable tRNAs. Analysis of tRNA modification and tRNA isoacceptor abundance revealed growth phase-dependent changes, particularly in anticodon stem-loop modifications that influence synonymous codon translation. Changes in queuosine levels preceded shifts in ribosomal proteins, suggesting a contribution to codon-biased translation. Collectively, these findings reveal growth phase-associated remodeling of the <i>E. faecalis</i> tRNA pool and support a model in which queuosine-dependent translational reprogramming shapes protein expression during bacterial growth.IMPORTANCE<i>Enterococcus faecalis</i> is a common cause of hospital-acquired infections. Despite its clinical importance, a comprehensive understanding of the organism's physiology and adaptation to environmental changes remains incomplete. Here, we characterized protein, transcript, and tRNA dynamics across bacterial growth phases, uncovering a role for posttranscriptional regulation marked by tRNA reprogramming and biased synonymous codon usage. These findings enhance our understanding of <i>E. faecalis</i> growth and support a model of translational reprogramming therein.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0147426"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865600","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":"Extension of host lifespan by polyamines derived from gut bacteria.","authors":"Hiromi Shimokawa, Emil Salim, Aki Hori, Tsuyoshi Fujita, Hayato Takihara, Hibiki Kadoguchi, Yuki Kontani, Rika Hirano, Mitsuharu Matsumoto, Shujiro Okuda, Takayuki Kuraishi, Shin Kurihara","doi":"10.1128/mbio.01484-26","DOIUrl":"10.1128/mbio.01484-26","url":null,"abstract":"<p><p>Metabolites produced by gut bacteria are taken up by the host and have a direct impact on its health. However, to our knowledge, no studies have investigated the effects of gut bacterial metabolites on the lifespan of the host using gnotobiotic animals colonized with gut bacteria deficient in biosynthetic genes involved in the production of specific metabolites. Polyamines, such as putrescine and spermidine, are among the most important metabolites of gut bacteria. Previous studies have shown that increasing polyamines in the colon of mice extends their lifespan and biological functions. In this study, we produced gnotobiotic flies colonized with <i>Escherichia coli</i>, in which polyamine biosynthetic genes were deleted or complemented. Gnotobiotic flies were fed a polyamine-free diet, and the effects of metabolites derived solely from gut bacteria on the lifespan of the host were analyzed. The results showed that polyamines derived from gut bacteria significantly prolonged the lifespan of the flies. Furthermore, the expression of <i>TotM</i> and <i>Halo</i> was suppressed in flies monocolonized with polyamine-producing <i>E. coli</i> compared with those monocolonized with mutant bacteria incapable of producing polyamines.IMPORTANCEThe intestinal tract of a human contains more than 150 species of gut bacteria, which comprise the gut microbiota. Only a very small number of gut bacteria, compared to the bacteria in feces, can come into contact with human tissues due to the barrier mechanism of the intestinal tract, but metabolites of the gut microbiota can pass through the intestinal epithelium and be taken into the body, directly affecting the health of the host. Thus, the importance of gut bacterial metabolites has received increasing attention in recent years. However, analysis into the effects of gut bacterial metabolites on host animals has been limited to only part of the host animal life cycle. In this study, we used <i>Drosophila melanogaster</i>, which has a short average lifespan, as a host and measured its lifespan to provide a simple analysis of the lifetime effects of gut bacterial metabolites on the host.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0148426"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920248","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":"Adherent-invasive <i>Escherichia coli pduB</i> drives vitamin B₁₂-dependent colitis in mice.","authors":"Shahanshah Khan, Jungyeon Kim, Alexander Lafrance, Sydney Field, Xi Li, Lisa N Kinch, Kevin J Forsberg, Tamia A Harris-Tryon, Qian Cong, Kim Orth, Hans-Christian Reinecker, Josephine Ni","doi":"10.1128/mbio.01698-26","DOIUrl":"10.1128/mbio.01698-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Adherent-invasive &lt;i&gt;Escherichia coli&lt;/i&gt; (AIEC) are strongly implicated in the pathogenesis of Crohn's disease, but the virulence factors driving their invasive and pro-inflammatory behavior remain incompletely defined. Here, we demonstrate that vitamin B&lt;sub&gt;12&lt;/sub&gt; availability modulates &lt;i&gt;pdu&lt;/i&gt;-dependent AIEC virulence. The 1,2-propanediol utilization (&lt;i&gt;pdu&lt;/i&gt;) operon, which requires vitamin B&lt;sub&gt;12&lt;/sub&gt; as a cofactor, has previously been associated with bacterial virulence. Here, we validated this association and demonstrated its functional relevance in mouse models of colitis. Deletion of &lt;i&gt;pduB&lt;/i&gt;, a structural component of the &lt;i&gt;pdu&lt;/i&gt; microcompartment, in the prototypical AIEC strain NRG857c impaired invasion of intestinal epithelial cells without affecting bacterial growth, biofilm formation, or intestinal colonization. In contrast, &lt;i&gt;pduB&lt;/i&gt; deletion reduced mucosal association and significantly attenuated colitis in &lt;i&gt;Il10&lt;sup&gt;-/&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;-&lt;/sup&gt; mice. Moreover, loss of &lt;i&gt;pduB&lt;/i&gt; protected against AIEC-induced epithelial barrier dysfunction and reduced expression of pro-inflammatory cytokines, including &lt;i&gt;Il6&lt;/i&gt;, &lt;i&gt;Il1b&lt;/i&gt;, and &lt;i&gt;Tnf-a&lt;/i&gt;. Unexpectedly, &lt;i&gt;pduB&lt;/i&gt; deletion was associated with elevated host serum vitamin B&lt;sub&gt;12&lt;/sub&gt; levels, and exogenous vitamin B&lt;sub&gt;12&lt;/sub&gt; supplementation directly inhibited AIEC invasion &lt;i&gt;in vitro&lt;/i&gt; and effectively protected &lt;i&gt;Il10&lt;sup&gt;-/&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;-&lt;/sup&gt; mice from AIEC-induced colitis. Furthermore, vitamin B&lt;sub&gt;12&lt;/sub&gt;-mediated suppression of AIEC invasion and barrier dysfunction was dependent on an intact &lt;i&gt;pdu&lt;/i&gt; pathway. Together, these findings establish &lt;i&gt;pduB&lt;/i&gt; as a key regulator of AIEC virulence. Our findings identify vitamin B&lt;sub&gt;12&lt;/sub&gt; availability as a host-modifiable factor that influences AIEC pathogenicity, suggesting potential therapeutic strategies for AIEC-driven intestinal inflammation in Crohn's disease.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;In this study, we demonstrated that vitamin B&lt;sub&gt;12&lt;/sub&gt; availability modulates a metabolic interaction between adherent-invasive &lt;i&gt;Escherichia coli&lt;/i&gt; (AIEC) and the host micronutrient vitamin B&lt;sub&gt;12&lt;/sub&gt; that influences AIEC epithelial invasion. We confirm that a gene within the 1,2-propanediol utilization pathway (&lt;i&gt;pduB&lt;/i&gt;) is critical for AIEC invasion and the development of intestinal inflammation in multiple mouse models. We further identify that vitamin B&lt;sub&gt;12&lt;/sub&gt;, a cofactor for metabolic reactions within the Pdu microcompartment, is altered in the host during infection, suggesting changes in the microbe-host vitamin B&lt;sub&gt;12&lt;/sub&gt; utilization dynamics. Functionally, we also show that vitamin B&lt;sub&gt;12&lt;/sub&gt; supplementation significantly inhibited AIEC invasion of epithelial cells &lt;i&gt;in vitro.&lt;/i&gt; Lastly, we found that vitamin B&lt;sub&gt;12&lt;/sub&gt; supplementation provided strong protection against AIEC-induced colitis in &lt;i&gt;Il10&lt;sup&gt;-/&lt;/sup&gt;&lt;/i&gt;&lt;sup&gt;-&lt;/sup&gt; mice, preventi","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0169826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977086","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":"CysK2 couples copper sensing to redox adaptation in <i>Mycobacterium tuberculosis</i>.","authors":"Wendy Le Mouëllic, Florence Levillain, Ting-Di Wu, Gérald Larrouy-Maumus, Frédéric Lagarrigue, Edith Vidal, Yoann Rombouts, Yannick Poquet, Olivier Neyrolles","doi":"10.1128/mbio.00816-26","DOIUrl":"10.1128/mbio.00816-26","url":null,"abstract":"<p><p>Copper is recognized as a host-derived cue encountered by <i>Mycobacterium tuberculosis</i> and other microbes during infections, yet the magnitude, intracellular distribution, and physiological consequences of this exposure remain incompletely understood. Here, we combined high-resolution imaging, transcriptomic profiling, intracellular reporter assays, and mouse infection models to define how <i>M. tuberculosis</i> responds to physiologically relevant copper levels during infection. NanoSIMS analysis showed that copper reaches intracellular bacilli and accumulates in discrete phosphorus-rich foci in bacteria. Exposure to physiological copper concentrations <i>in vitro</i> triggered a highly specific transcriptional response dominated by the copper-inducible CsoR and RicR regulons. The RicR-regulated <i>cysK2</i> gene, encoding the (<i>S</i>-sulfo)cysteine synthase CysK2, was one of the most strongly induced loci. In infected macrophages, <i>cysK2</i> expression was modulated by extracellular copper availability, host copper transport pathways, and hypoxia. <i>In vivo</i>, the H37Rv <i>cysK2</i>-deficient mutant showed reduced long-term persistence in mice and a shift toward a more oxidized redox potential. Together, these findings identify CysK2 as a copper-responsive effector linking host-derived copper sensing to redox homeostasis and contributing to long-term persistence during infection.IMPORTANCESuccessful infection by <i>Mycobacterium tuberculosis</i> depends on its ability to detect and adapt to host-imposed changes in the phagosomal environment. Our work shows that copper contributes to this adaptation not simply by imposing toxicity, but by triggering a response that helps sustain bacterial fitness within host cells. We identify CysK2 as a key component of this response, linking copper sensing to sulfur metabolism, redox balance, and persistence during infection. These findings shift the view of copper from a purely antimicrobial factor to a host-derived environmental signal that remodels <i>M. tuberculosis</i> physiology, and they uncover a new mechanism by which the pathogen maintains intracellular survival.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0081626"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906638","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":"Craig Venter, a microbiologist.","authors":"Rino Rappuoli","doi":"10.1128/mbio.01732-26","DOIUrl":"10.1128/mbio.01732-26","url":null,"abstract":"<p><p>The scientific career of Craig Venter, who pioneered genomics, big data, and synthetic biology, has been a turning point in biology. His science will continue to influence the world forever. He will be remembered for the first genome of a living organism, for the human genome, and for the first fully synthetic bacterial chromosome. I was fortunate to walk part of an amazing journey with Craig and experience first-hand what visionary science is and what it can lead to for the benefit of humankind. In this article, I make the case that Craig should be remembered also for his revolutionary contribution to microbiology and vaccinology. Indeed, he was the first to sequence a bacterial genome and the first to get a glimpse of the almost infinite diversity of the microbial world, and he pioneered the transition from conventional to modern vaccinology by introducing genomics and synthetic biology.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0173226"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990483","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":"Serotype-independent inhibition of <i>S. pneumoniae</i> by SMiTE, a commensal-derived bacteriocin.","authors":"João Lança, Joana Bryton, João Borralho, Catarina Candeias, Wilson Antunes, Amir Pandi, Raquel Sá-Leão","doi":"10.1128/mbio.01703-26","DOIUrl":"https://doi.org/10.1128/mbio.01703-26","url":null,"abstract":"<p><p><i>Streptococcus pneumoniae</i> remains a leading cause of disease despite widespread vaccination, highlighting the need for serotype-independent strategies. We recently identified commensal streptococci that produce bacteriocins with anti-pneumococcal activity. Here, we evaluate these bacteriocins as candidates for pneumococcal control. Using cell-free protein synthesis, we screened 58 bacteriocins, the majority of which absent in available pneumococcal genomes, and identified SMiTE as the most potent. Purified SMiTE disrupted pneumococcal membrane integrity, as shown by confocal, transmission, and scanning electron microscopy, induced ATP leakage, and triggered transcriptional responses consistent with envelope stress and metabolic remodeling. In a mouse nasopharyngeal colonization model, intranasal SMiTE treatments reduced pneumococcal loads by 65-fold with no significant weight loss. SMiTE inhibited a broad range of serotypes, with the strongest activity against serotype 3, which is poorly controlled by current vaccines, while sparing most oral and upper respiratory tract commensals. Repeated sub-inhibitory exposure did not select resistant mutants in line with the membrane-targeting mechanism. These findings establish SMiTE as a commensal-derived strategy for serotype-independent, microbiota-sparing pneumococcal decolonization.IMPORTANCE<i>Streptococcus pneumoniae</i> is a bacterium that can cause serious infections such as pneumonia, meningitis, and bloodstream infections. Although vaccines have greatly reduced disease, they do not protect against all strains, making new approaches urgently needed. In this study, we discovered a natural antimicrobial molecule, called SMiTE, produced by harmless bacteria that normally live in the human mouth. SMiTE effectively kills pneumococci by damaging their protective membrane, preventing them from surviving. In mice, a simple nasal treatment with SMiTE dramatically reduced the amount of pneumococci in the nose, where these bacteria first establish themselves before spreading or causing disease. Importantly, SMiTE was active against many different pneumococcal strains, including serotype 3, which is poorly controlled by current vaccines, while leaving most beneficial bacteria unharmed. Because it did not readily trigger resistance, SMiTE represents a promising new strategy to prevent pneumococcal carriage, transmission, and disease, regardless of serotype.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0170326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167045","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":"Adaptive landscape of the metallo-β-lactamase NDM-1 to emerging β-lactam-based therapies.","authors":"Fernanda D Romero, Salvador I Drusin, Guillermo Bahr, Gastón González, Robert A Bonomo, Diego M Moreno, Lisandro J González, Alejandro J Vila","doi":"10.1128/mbio.02280-26","DOIUrl":"https://doi.org/10.1128/mbio.02280-26","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The New Delhi metallo-β-lactamase (NDM) is a major determinant of carbapenem resistance. This has prompted the development of novel therapeutic strategies to treat NDM producers. Since these therapies impose new selective pressures, their clinical deployment may favor NDM variants carrying escape mutations. To anticipate these events and inform therapeutic decisions, we explored the evolutionary landscape of NDM-1 under different selective constraints. To this end, we generated a diverse library of &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;NDM&lt;/sub&gt; variants and challenged it with zinc starvation, antibiotics, or β-lactam/β-lactamase inhibitor combinations that represent novel and emerging therapies. Selection under zinc limitation and cefotaxime identified mutational trajectories that recapitulate clinical NDM evolution, validating the diversity of the library and its predictive nature. Drug-specific selections revealed sharply different evolutionary pathways. Mecillinam selected a narrow evolutionary pathway centered on residues N220 and M67, which enhance productive active-site interactions with this penicillin. Cefepime/taniborbactam selected multiple escape routes, dominated by substitutions at E152 and, secondarily, K211, that impair productive interaction with taniborbactam. In contrast, cefiderocol/xeruborbactam under iron-depleted conditions and aztreonam/avibactam did not select NDM variants conferring an improved resistance phenotype in the tested &lt;i&gt;Escherichia coli&lt;/i&gt; background. These results show that NDM evolution is constrained by the chemistry of each therapeutic challenge. Substrate adaptation is possible for mecillinam, inhibitor escape is readily accessible for taniborbactam, whereas no NDM-centered escape was detected for the aztreonam- and xeruborbactam-based conditions tested. Mapping drug-specific NDM-centered landscapes can identify therapies that readily select enzyme-level escape and those for which resistance is more likely to require mechanisms beyond &lt;i&gt;bla&lt;/i&gt;&lt;sub&gt;NDM&lt;/sub&gt; sequence variation.IMPORTANCECarbapenem-resistant infections by Enterobacterales are increasingly difficult to treat because bacteria can destroy some of the most powerful antibiotics used in the clinic. This study focuses on &lt;i&gt;Escherichia coli&lt;/i&gt; carrying variants of the New Delhi metallo-β-lactamase (NDM), an enzyme that enables bacteria to resist carbapenem antibiotics. New therapies are being developed to overcome this problem, but bacteria may evolve again when exposed to these treatments. Here, we tested how New Delhi metallo-β-lactamase can adapt under the evolutionary pressure of last-resort therapies. The results show that not all treatments carry the same evolutionary risk. Some drugs allow the enzyme to adapt through specific mutations, whereas other combinations did not yield improved NDM variants in the tested bacterial background. This work identifies which treatments readily select changes within NDM and which may require resistance mechanisms else","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0228026"},"PeriodicalIF":5.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167908","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":"Orchestration of <i>S. aureus</i> EV biogenesis by nutrient availability through quorum sensing.","authors":"Clariss Limso Yamamoto, Meta Kuehn","doi":"10.1128/mbio.01598-26","DOIUrl":"https://doi.org/10.1128/mbio.01598-26","url":null,"abstract":"<p><p>The release of extracellular vesicles (EVs) is a universally conserved process. Bacterial EVs package diverse cargo, including proteins and nucleic acids, and influence bacterial adaptation and survival, as well as host-pathogen interactions. Currently, our understanding of the mechanisms underlying global principles of EV biogenesis and release in <i>Staphylococcus aureus</i> and in gram-positive species, in general, is limited. Here, we describe a moderately high-throughput approach to analyze the Nebraska Transposon Mutant Library to broadly identify determinants of <i>agr</i>-dependent EV production in <i>S. aureus</i>. We show that the <i>agr</i> quorum-sensing system dictates EV production in response to nutrient availability, likely through communication with the adaptive stress response. This study demonstrates the contribution of nutritional stress to EV biogenesis and supports a conserved communication strategy that allows metabolic state to influence EV production.IMPORTANCEStudies have demonstrated a role for gram-positive extracellular vesicles (EVs) in virulence and adaptation; however, mechanistic knowledge of EV biogenesis remains limited. Here, using a screening approach, we demonstrate how the downstream targets of the <i>agr</i>-quorum-sensing system in <i>Staphylococcus aureus</i>, α-PSMs and RNAIII, differentially contribute to and alter EV biogenesis. We show a likely conserved communication strategy that allows nutrient availability to influence EV production. Additionally, we identified numerous candidate genes potentially involved in EV biogenesis and its regulation, providing a valuable resource for future mechanistic studies.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0159826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166127","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":"Metaplasia creates a permissive niche for select <i>Fusobacterium</i> species in the stomach.","authors":"Camilo Gómez-Garzón, Valerie P O'Brien, Qiwen Chen, Katherine S Garman, Nina R Salama","doi":"10.1128/mbio.01747-26","DOIUrl":"https://doi.org/10.1128/mbio.01747-26","url":null,"abstract":"<p><p>Infection with <i>Helicobacter pylori</i> is the major risk factor for gastric cancer worldwide; yet the exact mechanisms behind this link remain unclear. <i>H. pylori</i>-associated tissue changes often disrupt the gastric microbiome, enabling secondary gastric colonization by oral bacteria. Among these secondary colonizers, <i>Fusobacterium</i> species have documented associations with several gastrointestinal cancers. We found that both <i>F. animalis</i> and <i>F. nucleatum</i> invade cultured human gastric adenocarcinoma cells, but <i>F. animalis</i> exhibited higher adherence and invasion, and hypoxic conditions promoted higher bacterial survival. Both adherence and invasion were inhibited by exogenous GalNAc, a glycan commonly observed in membrane glycoproteins of adenocarcinoma cells and a target of the fusobacterial adhesin Fap2. Using a mouse model of stomach metaplasia, we found that <i>F. animalis</i> colonized gastric tissue only after metaplasia onset, growing in multispecies biofilms in the mucus layer, while <i>F. nucleatum</i> colonized neither healthy nor metaplastic gastric tissue. Metaplasia led to upregulation of Gal-GalNAc in the stomach, and reduced gastric acidity allowed higher <i>F. animalis</i> loads in this model. By contrast, inflammation and the presence of <i>H. pylori</i> did not significantly influence stomach colonization by <i>F. animalis</i>. Further assessment of additional <i>Fusobacterium</i> species and strains revealed that whereas all tested species can invade gastric cancer cells <i>in vitro</i>, only <i>F. animalis</i> and <i>F. polymorphum</i> robustly colonize the metaplastic gastric tissue of the mouse model similar to <i>F. animalis</i>. Overall, our data support a model in which <i>H. pylori</i>-induced metaplasia makes the stomach susceptible to secondary infection by other cancer-associated microbes, including some <i>Fusobacterium</i> species.IMPORTANCE<i>Helicobacter pylori</i> infection is the primary risk factor for gastric cancer worldwide, yet the underlying cancer-promoting mechanisms are not fully defined. Our study shows that metaplasia, a precancerous condition typically triggered by <i>H. pylori</i> and characterized by specific changes in gene expression and tissue remodeling, can enable secondary infection by other cancer-associated bacteria. Specifically, we found that certain species of the genus <i>Fusobacterium</i>, linked to several gastrointestinal cancers, colonize the stomach only after the onset of metaplasia. Metaplasia-associated changes in the stomach include altered surface sugars and reduced acidity, which together may create a more permissive environment for bacterial growth. Our findings support a model in which disruptions of gastric tissue architecture induced by chronic <i>H. pylori</i> infection facilitate colonization by other cancer-related bacteria, contributing to the growing body of evidence highlighting the role of bacteria in cancer development.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0174726"},"PeriodicalIF":5.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137530","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}