mBio最新文献

{"title":"Targeting conserved interaction surfaces of alphavirus nsP4 supports the rational design of live-attenuated vaccine candidates.","authors":"Xiaoyao Yang, Evelin Väljaots, Kaiyu Li, Krystyna Naumenko, Sandra Koit, Yaw Bia Tan, Xiang Liu, Victor Rodrigues de Melo Costa, Suresh Mahalingam, Dahai Luo, Andres Merits, Jian Yang","doi":"10.1128/mbio.01638-26","DOIUrl":"10.1128/mbio.01638-26","url":null,"abstract":"<p><p>Alphaviruses are emerging arboviruses that pose a growing threat to global public health; however, effective interventions remain limited. Recent structural studies of the chikungunya virus (CHIKV) replicase core revealed that the viral RNA-dependent RNA polymerase nsP4 interacts with both nsP1 and nsP2 and is predicted to engage viral RNA. The conservation and multifunctionality of nsP4 make it a challenging but promising target for rational attenuation. Here, we evaluated 58 structure-guided mutations in nsP4 predicted to disrupt interactions with nsP1, nsP2, or viral RNA using a <i>trans</i>-replicase system. Sixteen selected mutations were further analyzed in a CHIKV-o'nyong-nyong virus chimera and Semliki Forest virus (SFV). Most mutants were viable but showed varying degrees of attenuation in mammalian and mosquito cells. Viruses carrying mutations in predicted RNA-interaction sites frequently acquired pseudoreversions and/or second-site compensatory changes, whereas those harboring mutations affecting nsP1 or nsP2 interfaces were more genetically stable. Three substitutions representing defects in nsP1 interaction (F164A), predicted RNA interaction (K174S), and nsP2 interaction (D393A) were further characterized in authentic CHIKV and displayed attenuation consistent with that observed in SFV. <i>In vivo</i>, all three variants showed reduced pathogenicity in the SFV mouse model, with F164A being avirulent, immunogenic, and conferring complete protection against lethal challenge. In a CHIKV mouse model, these mutations attenuated disease and reduced serum virus titers and inflammatory cell infiltration. Together, these findings provide a molecular framework for the rational design of live-attenuated alphavirus vaccine candidates and support broader evaluation of nsP4-based attenuation.</p><p><strong>Importance: </strong>Alphaviruses are an increasing global health concern, with hundreds of thousands of chikungunya cases reported worldwide in 2025; however, vaccine options remain limited, and no specific antiviral treatment is available. Recent structural studies have revealed conserved functional interfaces in the viral RNA polymerase nsP4, but their value for attenuation had not been systematically explored. Here, using structure-guided mutagenesis, validation in multiple viral systems, and <i>in vivo</i> analysis, we show that selected nsP4 mutations can strongly attenuate replication and pathogenicity while preserving immunogenicity. These findings identify conserved nsP4 interfaces as a shared vulnerability of alphaviruses and provide a molecular framework for the rational design of broadly applicable live-attenuated vaccines while also highlighting nsP4 as a functionally constrained target relevant to antiviral development.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0163826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920213","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":"A protective hybrid protein vaccine informed by mapping major histocompatibility class II epitopes in <i>Cryptococcus neoformans</i> chitin deacetylases that stimulate CD4⁺ T-cell responses.","authors":"Charles A Specht, Lorena V N Oliveira, Diana Carlson, Maureen M Hester, Satya Sahu, Gabriel Kristian Pedersen, Stuart M Levitz","doi":"10.1128/mbio.02176-26","DOIUrl":"10.1128/mbio.02176-26","url":null,"abstract":"<p><p>Infections due to <i>Cryptococcus</i> species are estimated to cause over 100,000 deaths a year. No cryptococcal vaccines are approved for human use. We have shown that vaccine formulations consisting of <i>C. neoformans</i> chitin deacetylase 2 (Cda2) and Cda1 adjuvanted with Cationic Adjuvant Formulation 01 (CAF01) protect mice against experimental cryptococcosis by a mechanism dependent upon CD4⁺ T cells. Here, using overlapping peptide libraries, we mapped epitopes in Cda2 and Cda1 that stimulated interferon-gamma (IFNγ) release from splenocytes of C57BL/6 and DR4 mice immunized with these proteins. DR4 mice lack mouse major histocompatibility class II (MHC-II) proteins and express chimeric MHC-II proteins with the specificity of the human HLA-DR allele, HLA-DRB1*04:01. Experimental results were then compared with MHC-II binding predictions using the Immune Epitope Database NetMHCIIpan 4.1 BA MHC-II epitope prediction tool. Unique epitopes in Cda2 and Cda1 were discovered for each mouse strain, some of which were not predicted to bind well to MHC-II. CD4⁺ T cells were responsible for cytokine release as IFNγ production was lost if CD4⁺ T cells were depleted from the splenocyte population. Finally, we tested a hybrid recombinant protein that consisted of portions of Cda2 and Cda1 containing the MHC-II/CD4⁺ T-cell epitopes that induce CD4⁺ T cells in DR4 mice. When administered as a CAF01-adjuvanted vaccine, the hybrid protein protected DR4 mice from an otherwise lethal <i>C. neoformans</i> pulmonary challenge. These results provide a proof of principle regarding the utility of MHC-II/CD4⁺ T-cell epitope mapping in cryptococcal vaccine development.</p><p><strong>Importance: </strong>The development of vaccines to prevent cryptococcosis, a fungal disease which causes over 100,000 deaths annually, is a public health priority. We have demonstrated that adjuvanted vaccines containing two <i>Cryptococcus neoformans</i> protein antigens, chitin deacetylase (Cda)2 and Cda1, protect mice against experimental cryptococcosis by a mechanism dependent upon CD4⁺ T cells. In this study, we determined which 15-amino-acid peptides of Cda2 and Cda1 stimulate CD4⁺ T cells in C57BL/6 and DR4 mice; the latter mouse strain has human major histocompatibility class II (MHC-II) specificity. We then synthesized a small hybrid protein containing those portions of Cda2 and Cda1 that strongly stimulated CD4⁺ T-cell responses in DR4 mice. As an adjuvanted vaccine, the hybrid Cda2/1 protein protected DR4 mice from a <i>C. neoformans</i> pulmonary challenge. Thus, CD4⁺ T-cell/MHC-II epitope mapping experimentally validated the design of a protective multi-epitope protein for use in cryptococcal vaccines.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0217626"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182853","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":"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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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":"","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":"","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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducible cysteine synthesis by CysK2 provides copper resistance in <i>Mycobacterium tuberculosis</i>.","authors":"Daisy X Ji, Nicholas R Silvaggi, Anna Benko, K Heran Darwin","doi":"10.1128/mbio.00888-26","DOIUrl":"10.1128/mbio.00888-26","url":null,"abstract":"<p><p>Copper is an essential nutrient that at high levels is toxic to life. Mammalian hosts can accumulate copper in phagolysosomes to restrict a variety of pathogens, including <i>Mycobacterium tuberculosis</i>. However, pathogens have evolved various mechanisms to counter copper stress. While several pathways that mitigate copper-derived toxicity have been described in <i>Mycobacterium tuberculosis</i>, the <i>Mycobacterium tuberculosis</i> lab strain H37Rv is significantly more sensitive to copper than other lab strains, including CDC1551 and Erdman. Here, we determine a cause of this sensitivity in H37Rv is due to a single amino acid substitution in CysK2 (Rv0848), which is encoded in the copper-inducible RicR regulon required for robust copper resistance and virulence. H37Rv CysK2 was previously reported as a S-sulfocysteine synthase. However, we found CysK2 is a cysteine synthase, the activity of which is required for resistance to copper. This study is the first to link <i>de novo</i> cysteine biosynthesis with copper resistance in <i>Mycobacterium tuberculosis</i>.</p><p><strong>Importance: </strong>Copper is a proposed component of the host immune response against <i>Mycobacterium tuberculosis</i>; thus, an understanding of how this pathogen mitigates copper stress may yield new targets for therapeutics. Cysteine synthesis is implicated in copper responses in other bacterial species, but had not been shown in mycobacterial copper resistance. This study demonstrates for the first time that the <i>Mycobacterium tuberculosis</i> cysteine synthase CysK2 and, by extension, cysteine biosynthesis, can promote copper resistance.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0088826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604713","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":"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":"","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":"","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":"","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":"","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":"","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":"","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}