mBio最新文献

{"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}

{"title":"mGem: Bacterial aversion to making new genes.","authors":"Md Hassan Uz-Zaman, Howard Ochman","doi":"10.1128/mbio.02016-26","DOIUrl":"https://doi.org/10.1128/mbio.02016-26","url":null,"abstract":"<p><p>All genes must ultimately have arisen <i>de novo</i> from non-coding sequences, but to what extent is this process an ongoing contributor to the contents of contemporary genomes? Based on the expansive pangenome of <i>Escherichia coli</i>, genes created <i>de novo</i> are short-lived and have made virtually no contribution to the set of longer, conserved genes that form the bulk of the canonical gene repertoire. Due to the generality of bacterial genome dynamics, this trend likely applies across taxa, suggesting that the vast majority of truly novel genes were created in the deep evolutionary past, thereby consigning the role of the newly invented genes to transient adaptive challenges.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0201626"},"PeriodicalIF":5.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136775","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":"The dependence of Rev-mediated nuclear export of EIAV mRNA on Rev multimerization is modulated by mRNA length.","authors":"Weiwei Ma, Mengmeng Zhang, Xiangmin Zhang, Liuke Sun, Jiwei Li, Yang Zhao, Xiaohua Ma, Weiguo Zhang, Bowen Bai, Xue-Feng Wang, Xiaojun Wang","doi":"10.1128/mbio.00841-26","DOIUrl":"https://doi.org/10.1128/mbio.00841-26","url":null,"abstract":"<p><p>All lentiviruses encode a regulatory protein, Rev, which mediates nuclear export of viral mRNAs and is required for viral replication, and multimerization of Rev is thought to be critical for its function. The lentivirus equine infectious anemia virus (EIAV) Rev is known to mediate the nuclear export of long-length, unspliced, or incompletely spliced viral mRNA encoding the viral structural proteins (Gag, Pol, and Env), like Rev from other lentiviruses. However, EIAV Rev also mediates the nuclear export of a short-length, fully spliced viral mRNA species encoding the functionally unknown protein Mat. Here, we found that disruption of Rev multimerization impaired Rev activity in mediating nuclear export and expression of <i>gag-pol</i> mRNA, but not in mediating nuclear export and expression of <i>mat</i> mRNA. Deficiency of Rev multimerization leads to lower viral replication. Further investigation revealed that the activity of multimerization-deficient Revs in mediating nuclear export and expression of long-length EIAV or HIV-1 mRNAs was significantly lower than that of wild-type Rev, while this difference was significantly reduced or absent between the two in mediating nuclear export and expression of short-length EIAV or HIV-1 mRNAs. This suggests that the differential dependence of the nuclear export of <i>gag-pol</i> mRNA and <i>mat</i> mRNA on Rev multimerization is modulated by the lengths of the mRNA species. Our findings suggest that when targeting short mRNAs, EIAV Rev appears to be able to perform nuclear export activity in a non-multimerized state.IMPORTANCEMultimerization of lentiviral Rev is thought to be essential for its function, which is to mediate nuclear export of viral mRNA, a necessary step in lentiviral replication. In equine infectious anemia virus (EIAV), the nuclear export of unspliced viral mRNAs encoding structural proteins (Gag/Pol) is dependent on Rev. Moreover, our recent studies have demonstrated that the nuclear export of a fully spliced mRNA species, <i>mat</i>, encoding a small protein (Mat) of unknown function, is also Rev-dependent. In this study, we observed that the expression and nuclear export of EIAV <i>gag-pol</i> mRNA were strictly dependent on Rev multimerization, whereas those of <i>mat</i> mRNA were not. Interestingly, we also determined that the dependence of Rev-mediated nuclear export of EIAV mRNA on Rev multimerization is strongly associated with lengths of these mRNA species. Our data imply that EIAV Rev is able to exert nuclear export activity in a non-multimerized state.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0084126"},"PeriodicalIF":5.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136835","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 <i>Salmonella</i>-specific protein enhances the antimicrobial peptide response of the PhoPQ two-component system.","authors":"Paris I Brown, Luke A F Barretto, Casey C Fowler","doi":"10.1128/mbio.01070-26","DOIUrl":"https://doi.org/10.1128/mbio.01070-26","url":null,"abstract":"<p><p><i>Salmonella enterica</i>, a major global pathogen, has evolved a distinctive pathogenesis that differs from related enteric pathogens. A central regulator of <i>Salmonella</i>-specific virulence gene expression is the broadly conserved PhoP/PhoQ (PhoPQ) two-component system. PhoPQ serves a distinct role in <i>Salmonella</i> compared to other species, suggesting a need to adapt its function for its unique and expanded role in this species. In this study, we identify a novel, <i>Salmonella</i>-specific component of the PhoPQ signaling system, a small putative lipoprotein we name PalA. We show that PalA localizes to the cytoplasmic membrane, where it interacts with PhoQ, leading to PhoP activation and a corresponding reprogramming of the PhoP regulon. PalA's transcriptomic impact is entirely PhoPQ-dependent, indicating strict specificity. Upon cationic antimicrobial peptide exposure, <i>palA</i> expression is induced, and it strongly activates PhoPQ, but <i>palA</i> shows low expression and has a minimal effect under low pH or low Mg²⁺ conditions, indicating its impact on PhoPQ is signal-specific. Notably, PalA does not stimulate PhoPQ systems from closely related species, indicating that <i>Salmonella</i> PhoPQ has adapted to promote its activation by PalA. Collectively, this study unveils an evolutionary adaptation by <i>Salmonella</i> that enhances its virulence gene expression in response to cationic antimicrobial peptide exposure.IMPORTANCE<i>Salmonella</i>, a major human pathogen, controls the expression of its virulence genes in part through the PhoP/PhoQ (PhoPQ) two-component system. In this study, we identify and characterize a novel component of this system: a small protein unique to <i>Salmonella</i>, which we name PalA. We show that exposure to cationic antimicrobial peptides (CAMPs), a host-derived signal encountered during infection, induces PalA expression. PalA then binds PhoQ, activating it and thereby enhancing virulence gene expression. This study reveals a previously overlooked component of the <i>Salmonella</i> PhoPQ signaling network, which is among the best-studied bacterial regulatory systems and has served as an important model system for understanding the regulation of bacterial pathogenesis. Furthermore, this work illustrates the important role small \"adaptor proteins\" can play in conferring new signaling properties to ancestral regulatory systems, in this case by boosting activity and the response to a specific environmental cue.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0107026"},"PeriodicalIF":5.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137492","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":"BR-bodies link RNA homeostasis to stress tolerance and intracellular fitness in <i>Brucella</i>.","authors":"Kaveendya S Mallikaarachchi, Rosemary Northcote, Thomas Kim, Melene A Alakavuklar, Vincent A Lawal, Vidhyadhar Nandana, Aretha Fiebig, Jared M Schrader, Sean Crosson","doi":"10.1128/mbio.01705-26","DOIUrl":"10.1128/mbio.01705-26","url":null,"abstract":"<p><p>Bacterial gene expression depends on the coordinated regulation of RNA synthesis, processing, and decay. The conserved RNA degradosome scaffold, ribonuclease E (RNase E), assembles into phase-separated bacterial ribonucleoprotein bodies (BR-bodies) through its C-terminal intrinsically disordered region (IDR). This IDR also scaffolds recruitment of degradosome client proteins that carry out post-transcriptional gene regulation. Whether BR-bodies regulate virulence programs to support infection, however, is largely undefined. We show that RNase E of the intracellular pathogen <i>Brucella ovis</i> forms RNA-dependent condensates <i>in vivo</i> and phase-separates with RNA <i>in vitro</i>, with the IDR necessary and sufficient for BR-body assembly. Deleting the IDR [<i>rne</i>(ΔIDR)] did not impair growth but sensitized <i>Brucella</i> to host-relevant oxidative and cell-envelope stressors. Transcriptome-wide profiling that simultaneously resolved mRNA decay and processing revealed that BR-bodies primarily accelerate mRNA turnover while stabilizing a distinct subset of transcripts. Notably, BR-bodies control the processing and levels of <i>virB</i> type IV secretion system mRNA and the turnover of its key activators, linking condensate-based RNA regulation to a core virulence pathway. Consistent with <i>virB</i> dysregulation, the <i>rne</i>(ΔIDR) mutant was severely attenuated in mammalian macrophages. To test whether phase separation is sufficient for BR-body function, we replaced the <i>B. ovis</i> IDR with the highly divergent <i>Caulobacter crescentus</i> IDR. This chimera assembled BR-bodies but rescued fitness incompletely, fully restoring oxidative-stress resistance but not cell-envelope stress resistance or intracellular fitness. BR-bodies therefore link RNA metabolism to <i>Brucella</i> stress resistance and infection, and their full function requires both phase separation and additional native IDR-specific activities, such as degradosome interactions.IMPORTANCEBiomolecular condensates are non-membrane-bound organelles that organize biological processes across all domains of life, but their role in bacterial infection is not well characterized. We show that <i>Brucella</i>, an intracellular bacterial pathogen and causative agent of the disease brucellosis, relies on biomolecular condensates called bacterial ribonucleoprotein bodies (BR-bodies) to control RNA stability and regulate gene expression. Without BR-bodies, <i>Brucella</i> is sensitized to host-relevant chemical stresses, cannot properly regulate essential infection machinery, and has severely diminished fitness within mammalian host cells. These results indicate that control of RNA levels by biomolecular condensates is required for <i>Brucella</i> survival within animal hosts, providing evidence that phase separation is a fundamental mechanism underlying <i>Brucella</i> adaptation to the hostile environment encountered during infection.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0170526"},"PeriodicalIF":5.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137485","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":"Fe(III) oxide respiration by a <i>Desulfovibrio</i> species lacking canonical outer-membrane electron transfer systems.","authors":"Qin Cheng, Dawn E Holmes, Dake Xu, Derek R Lovley","doi":"10.1128/mbio.02206-26","DOIUrl":"https://doi.org/10.1128/mbio.02206-26","url":null,"abstract":"<p><p><i>Desulfovibrio</i> species play an important role in the extracellular reduction of Fe(III) oxides and other metals in diverse environments, but their extracellular electron transfer (EET) mechanisms are poorly understood. We found that <i>Desulfovibrio</i> strain JY grew with H₂ or lactate as the electron donor and poorly crystalline Fe(III) oxide as the electron acceptor, demonstrating the capacity to conserve energy from Fe(III) respiration despite the absence of genes for porin-cytochrome conduits, outer-surface cytochromes, or electrically conductive pili. Washed cell suspensions reduced Fe(III) citrate at rates comparable to that of <i>Shewanella oneidensis</i>, demonstrating the ability to effectively reduce soluble extracellular electron acceptors at the cell surface. Strain JY reduced the extracellular electron shuttles anthraquinone-2,6-disulfonate (AQDS) and riboflavin, which stimulated Fe(III) oxide reduction. Culture filtrates accelerated Fe(III) oxide reduction, and the reduction of Fe(III) oxide sequestered within porous alginate beads confirmed the presence of a shuttle. Riboflavin accumulated during growth on Fe(III) oxide, and electrochemical analysis and flavin measurements indicated that it was the primary shuttle. Genes encoding homologs of the <i>S. oneidensis</i> flavin exporter Bfe were more highly expressed during Fe(III) oxide respiration than during sulfate reduction. These results demonstrate that <i>Desulfovibrio</i> strain JY conserves energy to support growth from Fe(III) oxide reduction with a self-produced flavin electron shuttle, but without the canonical outer-membrane <i>c</i>-type cytochromes typically associated with EET in gram-negative bacteria. The findings expand the known diversity of microbial Fe(III) oxide respiration mechanisms and suggest that current genome-based prediction methods may substantially underestimate the diversity of electroactive microorganisms in natural environments.IMPORTANCEFe(III) oxide reduction is an important biogeochemical process influencing the cycling of carbon, nutrients, trace metals, and contaminants in anaerobic soils and sediments. The capacity for Fe(III) oxide reduction is commonly inferred from the presence of genes encoding porin-cytochrome conduits and outer-surface <i>c</i>-type cytochromes. The finding that a gram-negative microbe lacking these components can conserve energy to support growth from the reduction of Fe(III) oxides suggests that there is a much broader diversity of microbes capable of extracellular electron transfer than is generally considered. Genome-based strategies for elucidating the distribution and activity of electroactive microbes need revision to accommodate the expanding understanding of the range of mechanisms for electron transfer to insoluble extracellular electron acceptors.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0220626"},"PeriodicalIF":5.4,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137463","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":"Peripheral microbial metabolites as indicators of gut microbiome disruption: systematic review and meta-analysis.","authors":"Taylor Kain, Eric Armstrong, Bryan Coburn","doi":"10.1128/mbio.01927-26","DOIUrl":"https://doi.org/10.1128/mbio.01927-26","url":null,"abstract":"<p><p>Gut microbiome disruption is often characterized by the loss of obligately anaerobic bacteria, which may lead to altered production of microbial metabolites that can be detected peripherally. The application of widely used sequencing-based microbiome analyses to clinical settings is limited by cost, turnaround time, and challenges with patients with very low stool output. Since some products of strictly bacterial metabolism are detectable in blood, peripheral metabolites may provide a rapid and scalable indicator of gut microbiome composition and function. We performed a systematic review and meta-analysis of studies reporting circulating microbial metabolites and gut microbiome composition to evaluate whether peripheral microbial metabolites could identify gut microbiome perturbation. Candidate metabolites were identified systematically across an independent set of studies reporting metabolite-microbiome associations, enabling the assessment of reproducibility across disease states and cohorts. We performed a meta-analysis of 19 human cohorts comprising 3,242 participants with paired blood metabolite and stool microbiome data. Anaerobe depletion (obligate anaerobe relative abundance <0.70) was associated with decreased plasma concentration of products of anaerobic microbial metabolism. Combinations of metabolites distinguished individuals with anaerobe-depleted microbiomes from those without. Circulating metabolite levels distinguished between cases and controls with similar performance as gut microbiome composition across a range of health/disease states and changed markedly within patients experiencing gut anaerobe depletion after antibiotic exposure. Circulating microbial metabolites are potentially informative indicators of gut microbiome disruption and may serve as a rapid and scalable method for patient stratification in clinical trials or acute care settings.<b>IMPORTANCE</b>Circulating microbial metabolites represent a practical and scalable approach to detecting significant gut microbiome disruption, particularly the loss of obligate anaerobes. Our findings suggest that metabolites capture compositional consequences of microbiome collapse, with performance comparable to direct microbiome profiling in distinguishing disease states. Enabling diagnostic enrichment and real-time monitoring of microbiome injury (e.g., during antibiotic use or critical illness) has potential implications for both clinical care and research, including the selection of patients for investigation of microbiome-targeted therapies. With further validation, circulating metabolites could provide an accessible surrogate for gut microbiome composition in settings where sequencing is impractical.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0192726"},"PeriodicalIF":5.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128047","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}