mBio最新文献

{"title":"Importance of the gonococcal MtrCDE efflux pump system in decreasing bacterial susceptibility to zoliflodacin: implications for future clinical treatment of gonorrhea.","authors":"Jacqueline T Balthazar, Concerta L Holley, Debayan Dey, Graeme L Conn, William M Shafer","doi":"10.1128/mbio.01943-26","DOIUrl":"10.1128/mbio.01943-26","url":null,"abstract":"<p><p>The continued emergence and spread of <i>Neisseria gonorrhoeae</i> strains expressing clinical resistance to ceftriaxone (CRO) have stimulated the discovery of new antibiotics to treat gonococcal infections. As the MtrCDE efflux pump system has been linked to the ability of gonococci to develop resistance to multiple antibiotics (e.g., beta-lactams and macrolides), we studied whether it could diminish gonococcal susceptibility to a recently Food and Drug Administration (FDA)-approved antibiotic (zoliflodacin [ZOL]). ZOL recognizes DNA gyrase differently from other antibiotics and will likely be used in the future to treat uncomplicated urogenital tract infections that are refractory to cure by CRO. Herein, we provide evidence that mutations impacting <i>mtrCDE</i> gene expression or MtrCDE efflux activity can decrease gonococcal ZOL susceptibility. Moreover, these activities add to resistance levels afforded by a resistance mutation in <i>gyrB</i>. Hence, the accumulation of mutations in <i>gyrB</i> and <i>mtr</i> genes may negatively impact the future clinical efficacy of ZOL.</p><p><strong>Importance: </strong>The newly Food and Drug Administration (FDA)-approved antibiotic zoliflodacin (ZOL) will likely soon be used worldwide to treat gonococcal infections that are refractory to cure with the sole remaining antibiotic used in empiric monotherapy, ceftriaxone (CRO). Here, we find that the level of gonococcal susceptibility to ZOL is linked to expression and function of the MtrCDE efflux pump. This suggests that the future use of this new antibiotic will be challenged by mutations that are already present in clinical strains, as well as by mutations in a ZOL target gene (<i>gyrB</i>). Based on our collective observations and to extend the duration of ZOL in treating gonorrhea, we propose that future work should be devoted to developing adjunctive therapies that diminish its export by the MtrCDE efflux pump system.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0194326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906801","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":"Real-time volatilomics reveals microbiota and pathogen fingerprints in the honey bee.","authors":"Mateusz Fido, Silvia Moriano-Gutierrez, Jiayi Lan, Aurélien Pirat, Léa Zufferey, Elisa Cappio Barazzone, Renato Zenobi, Philip Engel, Emma Slack","doi":"10.1128/mbio.01419-26","DOIUrl":"10.1128/mbio.01419-26","url":null,"abstract":"<p><p>Understanding the complex relationship between gut microbiota and their hosts often relies on invasive sampling techniques. Honey bees provide a tractable model for host-microbe studies. Here, we establish single-bee volatilomics using secondary electrospray ionization-high-resolution mass spectrometry (SESI-HRMS) to examine volatile organic compounds released to the air around an individual live honey bee. Specifically, we focused on the primary gut microbiota metabolites present in gnotobiotic bees. Our findings reveal distinct volatilome profiles in honey bees that depend on their gut bacterial colonization state. We cross-validated our findings using an established metabolomics technique, liquid chromatography-high-resolution mass spectrometry (LC-HRMS), to compare and contrast the metabolites detectable with each method. Finally, we assessed the ability of SESI-HRMS to detect colonization with the bee pathogen <i>Serratia marcescens</i>. By comparing the volatile signature of this bacterium grown in liquid culture with that of infected honey bee headspace, we identified overlapping compounds, including butane-2,3-diol, that were elevated in infected bees relative to uninfected controls. Non-invasive SESI-HRMS volatilomics, paired with LC-HRMS, therefore, have the potential to identify biomarkers of bee microbiome composition and infection at the level of individual insects. These biomarkers represent practical targets for the development of simple, field-ready diagnostic tools for monitoring pollinator health.</p><p><strong>Importance: </strong>Honey bees are vital to various ecosystems and human agriculture as globally present pollinators. Current declines in bee populations threaten crop productivity and biodiversity and are driven by many factors, including habitat loss, pesticides, and pathogenic infections. The findings presented in this work demonstrate how the analysis of volatile species can precisely detect products of metabolic activity coming from the honey bee and its associated gut microbial community. We were able to demonstrate how high-resolution mass spectrometry can be used to study the host-microbiota relationship on the level of an individual insect. This technique, combined with volatilomics, allowed us to outline a volatile signature of infection in honey bees, which could become a target for in-field beehive disease monitoring.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0141926"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912961","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: The two-decade evolution of <i>in vivo</i> coral microbiome manipulations.","authors":"Lauren Speare, Stephanie M Rosales","doi":"10.1128/mbio.01678-26","DOIUrl":"10.1128/mbio.01678-26","url":null,"abstract":"<p><p>Over the past two decades, microbiome manipulations have emerged as a strategy to bolster coral fitness. Here, we provide a timeline of two decades of research on <i>in vivo</i> coral microbiome manipulation studies aimed at improving coral health. A summary of coral hosts, probiotic taxa, and how experimental design varies across studies is synthesized to identify commonly used taxa and research gaps. This review highlights methodological challenges and identifies opportunities to advance probiotic development and translate microbial interventions into practical tools for coral restoration and reef management.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0167826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017232","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":"SepIVA has a function in activating the mycobacterial divisome, which is inhibited during DNA damage.","authors":"Anusuya Nepal, Gwyneth Untalan, Cara C Boutte","doi":"10.1128/mbio.01985-26","DOIUrl":"10.1128/mbio.01985-26","url":null,"abstract":"<p><p>Bacterial cell division is a tightly regulated process that is carried out by a complex of proteins called the divisome. These proteins are assembled in a defined sequential order. Upon assembly, the complex is allosterically activated, which stimulates septal peptidoglycan synthesis at the nascent septum. Bacteria inhibit division during DNA damage by blocking either divisome assembly or activation. While the regulation of cell division is known to be important during <i>Mycobacterium tuberculosis</i> infection, little is known about mycobacterial mechanisms of divisome function and regulation in DNA damage. By using <i>Mycobacterium smegmatis</i> as a model organism, we find here that divisome factor SepIVA is involved in septum initiation and that it is recruited to the mid-cell by FtsQ, but it is not a recruitment factor itself. We find that a <i>sepIVA</i> loss-of-function defect can be suppressed by overexpression of <i>ftsW</i>, supporting a role for SepIVA in activation of peptidoglycan synthesis within the divisome. When cell division is inhibited during DNA damage, we find that SepIVA is delocalized from the division site, while the septal localization of FtsZ, FtsQ, and FtsW is not impacted. We also find that the interaction between FtsQ and SepIVA is inhibited during DNA damage. Our results suggest that SepIVA is involved in the activation of septal synthesis during normal growth and show that the signaling to inhibit cell division during DNA damage involves inhibition of SepIVA's interaction with FtsQ.IMPORTANCECell division is critical for bacterial cells to propagate and cause infection. Despite its importance, division is a dangerous process as it requires building and subsequently hydrolyzing new cell wall material in a place where the chromosome typically resides. If cell division occurs before chromosome segregation is completed, or if cell wall metabolism is improperly regulated, then cell death results. The divisome is a protein complex that regulates cell division-coordinating it with the status of the chromosome and ensuring that the cell wall metabolic enzymes are carefully controlled. Many of the proteins in the divisome complex are highly conserved across bacterial phyla; however, the factor that stimulates the complex to activate and initiate cell wall synthesis is not widely conserved. Here, we study the activation of the divisome in <i>Mycobacterium smegmatis</i>, a model for cell physiology of <i>Mycobacterium tuberculosis</i>. We find evidence that SepIVA, a protein found only in Actinomycetota, promotes activation of peptidoglycan synthesis at the divisome in mycobacteria. We also show that the association of SepIVA with the divisome is blocked under DNA damage, when cell division is inhibited. These results provide a model for the regulation of cell division in mycobacteria in growth and stress and also provide insights into how bacteria with different types of septa may regulate division differently.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0198526"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149017315","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":"Dual-barrier mechanism of superinfection exclusion in Newcastle disease virus: nucleoprotein and hemagglutinin-neuraminidase cooperate to block secondary infection.","authors":"Kejia Lu, Xuhong Cao, Zhengwu Chang, Xi Wei, Sa Xiao, Zengqi Yang, Haijin Liu","doi":"10.1128/mbio.03545-25","DOIUrl":"https://doi.org/10.1128/mbio.03545-25","url":null,"abstract":"<p><p>Superinfection exclusion (SIE) is a well-documented phenomenon in virology, wherein a primary viral infection prevents subsequent infection by the same or closely related viruses through various mechanisms. This phenomenon has been observed with Newcastle disease virus (NDV), a member of the Paramyxoviridae family. However, the molecular mechanisms underlying NDV-mediated SIE remain unclear. In this study, we elucidate a dual-barrier mechanism of NDV-mediated SIE, involving both the nucleoprotein (NP) and the hemagglutinin-neuraminidase (HN) glycoprotein. Our findings demonstrate that NDV SIE is initiated within 2 h of primary infection and intensifies over time, independent of viral virulence and host cell type. The NP protein forms an early cytoplasmic barrier by sequestering incoming NP subunits, while HN-neuraminidase activity at the viral membrane cleaves sialic acid receptors, preventing secondary virion adsorption. Furthermore, our data reveal that NDV-mediated SIE is specific to intraspecies interactions and does not extend to heterologous viruses, such as vesicular stomatitis virus.IMPORTANCESuperinfection exclusion (SIE) is a crucial viral strategy for limiting co-infection and ensuring the dominance of a single viral strain. The identification of the dual-barrier mechanism in Newcastle disease virus (NDV), involving both the nucleoprotein (NP) and hemagglutinin-neuraminidase (HN) proteins, significantly enhances our understanding of viral defense mechanisms. By elucidating how SIE operates at both the cytoplasmic and membrane levels, this study not only provides a mechanistic framework for NDV interference but also opens avenues for therapeutic applications. The discovery that NP and HN act synergistically to block secondary infection presents new strategies for combating viral co-infection in veterinary medicine and potentially in human viruses. Furthermore, understanding the viral determinants involved in SIE could guide the development of antiviral therapies that exploit these mechanisms to prevent superinfection and reduce viral spread.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0354525"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182839","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":"Flagella are required to activate expression of aggregation factors necessary for T6SS-mediated competition in host-like conditions.","authors":"Lauren Speare, Liang Zhao, Morgan N Pavelsky, Aundre Jackson, Steph Smith, Bhavyaa Tyagi, Garrett C Sharpe, Madison Woo, Scott M Gifford, Alecia N Septer","doi":"10.1128/mbio.03970-24","DOIUrl":"10.1128/mbio.03970-24","url":null,"abstract":"<p><p>Bacteria employ antagonistic strategies to eliminate competitors of an ecological niche. Contact-dependent mechanisms, such as the type VI secretion system (T6SS), are prevalent in host-associated bacteria, yet we know relatively little about how T6SS+ strains make contact with competitors in highly viscous environments, such as host mucus. To better understand how cells respond to and contact one another in such environments, we performed a genome-wide transposon mutant screen of the T6SS-wielding beneficial bacterial symbiont, <i>Vibrio fischeri</i> MJ11, and identified two sets of genes that are conditionally required for killing. We found that surface modification and flagellar-associated genes do not affect T6SS directly and are therefore not required for interbacterial killing when cell contact is forced, yet are necessary for killing in high-viscosity liquid (hydrogel), where cell-cell contact must be biologically mediated. Quantitative transcriptomics revealed that <i>V. fischeri</i> significantly increases expression of both T6SS genes and cell surface modification factors upon transition from low- to high-viscosity media. Consistent with coincubation and fluorescence microscopy data, flagella are not required for T6SS expression in hydrogel. However, flagella were necessary to enhance expression of ~50% of the genome in hydrogel, including the surface modification genes identified in our screen and functional pathways important for host colonization, such as uptake of host-relevant iron and carbon sources, and nitric oxide detoxification enzymes. Our findings suggest that flagella play a key role when <i>V. fischeri</i> cells coordinately activate competitive strategies and host colonization factors, underscoring the significance of the physical environment in directing complex bacterial behaviors.IMPORTANCEThe physical environment has dramatic effects on bacterial behavior, but little is known about how mechanical signals impact antagonistic interactions. Symbiotic bacteria use molecular weapons to eliminate competitors for limited space within highly viscous host tissue and mucus. Previously, we found that a putative lipoprotein adhesin, TasL, and an unknown ligand are required to bring competitor cells within range of the T6SS weapon. Here, we found that mutations in flagella or predicted surface modification genes prevent TasL-mediated adhesion and killing in high viscosity. Transcriptomics revealed the flagella are required to coordinate expression of host colonization factors with the T6SS interbacterial weapon when transitioning from lower to higher viscosity conditions. These findings suggest that flagella may play a role in sensing mechanical signals, such as environmental viscosity, to enhance a symbiont's ability to successfully colonize the host while efficiently eliminating potential competitors from the host niche.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0397024"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829813","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 suite of eight <i>Toxoplasma gondii</i> effectors cooperates to activate the non-canonical NF-κB pathway.","authors":"Kenna Berg, Michael W Panas, Samarchith P Kurup, John C Boothroyd, Alex Rosenberg","doi":"10.1128/mbio.01652-26","DOIUrl":"10.1128/mbio.01652-26","url":null,"abstract":"<p><p>As a master of host-cell reprogramming, <i>Toxoplasma gondii</i> (<i>T. gondii</i>) tachyzoites manipulate diverse signaling networks to establish a niche permissive for long-term infection. While the parasite's subversion of canonical NF-κB signaling (p65/p50) is well established, how infection impacts the non-canonical NF-κB pathway has been largely unexplored. Here, we report that <i>T. gondii</i> infection induces nuclear accumulation of the non-canonical NF-κB subunits RelB and p52 in both human and murine fibroblasts. This response is conserved across both type I and type II parasite genetic backgrounds. We demonstrate that this reprogramming is dependent on the MYR1-mediated export of dense granule effectors. Mechanistically, <i>T. gondii</i> infection drives the depletion of the negative regulator TRAF3, leading to the stabilization of NF-κB-inducing kinase (NIK), phosphorylation of p100, and its subsequent processing into p52. Utilizing a panel of combinatorial knockout parasites, we reveal that no single effector is responsible for this phenotype. Instead, a suite of eight MYR1-dependent effectors, IST, NSM, HCE1/TEEGR, GRA16, GRA18, GRA24, GRA28, and GRA84, functions through a collaborative, additive network to drive most of the non-canonical response. These findings highlight a distributed regulatory strategy used by the parasite to overcome host transcriptional robustness and shape host signaling.</p><p><strong>Importance: </strong><i>Toxoplasma gondii</i> infects nearly one-third of the global population and establishes infection by extensively rewiring host immune signaling. While decades of work have focused on how the parasite modulates canonical NF-κB activity, whether it also engages the alternative, non-canonical arm of this pathway has remained unclear. Here, we show that <i>T. gondii</i> tachyzoites activate non-canonical NF-κB signaling, driving nuclear accumulation of RelB/p52 through MYR1-dependent effector export. Unexpectedly, no single effector is responsible. Instead, eight secreted proteins act cooperatively to enable NIK stabilization and engage the non-canonical NF-κB cascade, revealing a networked mode of immune control. This discovery highlights a regulatory logic evolved by the parasite to overcome host transcriptional robustness. Together, these findings identify non-canonical NF-κB activation as a new axis of host-parasite interaction and expand our understanding of how <i>T. gondii</i> reprograms central immune signaling circuits through multi-effector networks.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0165226"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840381","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":"MAIT cell responses to <i>Staphylococcus aureus</i> and sensitivity to HlgAB toxin are modulated by activation and tissue-dependent virulence effects.","authors":"Elisa J M Raineri, Caroline Boulouis, Elli Mouchtaridi, Vera Nilsén, Curtis Cai, Tobias Kammann, Juliette Tabusse, Takuya Sekine, Nicole Wild, Christian Constantz, Eoghann White, Thomas R Müller, Anne Marchalot, Sabrina Ferreira, Jyotsana Kaushal, Akhirunnesa Mily, Miriam Franklin, Elena Bonaiti, Mary-Lyn Eichhorn, John Bassett, Chris Stamper, Jeffrey Y W Mak, David P Fairlie, Chris Tibbitt, Anna Norrby-Teglund, Nicole Marquardt, Jenny Mjösberg, Carl Jorns, Jenny Driving, Edwin Leeansyah, Marcus Buggert, Johan K Sandberg","doi":"10.1128/mbio.00663-26","DOIUrl":"10.1128/mbio.00663-26","url":null,"abstract":"<p><p>Mucosa-associated invariant T (MAIT) cells are unconventional T cells with innate-like rapid antimicrobial effector functions and serve as resident sentinels at mucosal and non-mucosal barriers. However, their role in immune defense against <i>Staphylococcus aureus</i> and the impact of bacterial immune evasion mechanisms are incompletely understood. Here, we have investigated MAIT cell responses to <i>S. aureus</i> and the impact of its broadly expressed leukocidin toxin HlgAB on MAIT cell responses in different human tissue sites. MAIT cells respond to <i>S. aureus</i> with a complex polyfunctional profile spanning proinflammatory IL-17, TNF, and IFNγ, anti-inflammatory IL-10, plus granzymes A, B, and K, perforin, and granulysin. The quality of responses was influenced by the microbial dose and time of exposure and was dependent on both MR1-presented antigen and cytokine co-activation. CD56⁺ MAIT cells displayed stronger effector responses and higher HlgAB sensitivity compared to CD56⁻ cells. MAIT cells were partially resistant to HlgAB-toxicity compared to monocytes; blood-derived MAIT cells remained susceptible, whereas tonsillar MAIT cells showed minimal sensitivity. Notably, activation reduced the MAIT cell susceptibility to HlgAB, and such activation also afforded indirect protection to monocytes in co-cultures. The reduced susceptibility of tonsillar MAIT cells correlated with lower CCR2 and CXCR1 expression, a pattern shared with barrier tissues such as the lung and intestines. In conclusion, these findings indicate that MAIT cells exhibit tissue- and context-dependent responses to <i>S. aureus</i> and sensitivity to HlgAB-mediated immune evasion.</p><p><strong>Importance: </strong>Mucosa-associated invariant T (MAIT) cells are an evolutionarily conserved unconventional T cell subset that responds to riboflavin pathway-derived antigens from a range of microbes. Here, we found that the human MAIT cell response to the pathogen <i>S. aureus</i> is robust with the polyfunctional complexity influenced by bacterial concentration and response kinetics. The ubiquitously expressed <i>S. aureus</i> immune-evasive toxin HlgAB attacks MAIT cells via CCR2. However, the sensitivity of MAIT cells to HlgAB varies depending on tissue localization, where in particular tissue-resident MAIT cells in tonsils are resistant. Antigen-specific activation of MAIT cells reduces HlgAB sensitivity, with protection also afforded to monocytes in the vicinity. These findings uncover the complex and dynamic interaction between an evolutionarily conserved arm of immunity and immune evasion mechanisms of the important pathogen <i>S. aureus</i>.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0066326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990475","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":"Discovery and characterization of a pigment produced by <i>Streptococcus pyogenes</i>.","authors":"Sobita Pathak, Theo DeVinney, Artemis Gogos, Reginald A Woods, Caleb M Anderson, Jennifer C Chang, Michael J Federle","doi":"10.1128/mbio.01348-26","DOIUrl":"10.1128/mbio.01348-26","url":null,"abstract":"<p><p><i>Streptococcus pyogenes</i> is a major human-restricted pathogen capable of both localized and systemic diseases, as well as causing post-infectious acute and chronic rheumatological conditions. Despite its well-documented clinical importance and over a century of extensive research, gaps persist in understanding this pathogen. We report the discovery of a novel pigment produced by <i>S. pyogenes</i> when cultured in a replete, chemically defined medium. Color development accumulates during growth, requires exposure to oxygen, and remains associated with the bacterial cell. Though only 20% of a small strain collection produced the pigment (8 of 40), positive cultures were overrepresented by M1 and M89 serotypes. Given that pigments are critical virulence and fitness determinants in pathogens like <i>Staphylococcus aureus and Streptococcus agalactiae</i>, here, we describe initial attempts to characterize <i>S. pyogenes</i> pigment biosynthesis, regulation, and potential benefits to the organism. A total of 20,405 transposon mutants were screened for pigment loss in liquid culture, and we identified 94 independent hits enriched in pathways associated with isoprenoid biosynthesis, purine biosynthesis, guanosine transport, and mixed acid fermentation. Although color development requires oxygen, the extracted pigment did not provide antioxidative activity as compared with non-pigmented extracts. Pigment production was inhibited when the Rgg2/Rgg3 quorum-sensing system was active, though by an unknown mechanism. Treatment of RAW-Blue macrophages with the extracted pigment significantly reduced NFκB activation, suggesting a potential anti-inflammatory effect. Overall, this study describes a previously uncharacterized pigment produced by <i>S. pyogenes</i> and provides insights into its oxygen-dependent production and associated metabolic pathways.</p><p><strong>Importance: </strong><i>Streptococcus pyogenes</i> is a ubiquitous pathogen responsible for ~1.8 million severe infections and 500,000 deaths annually. This organism has not been recognized as a pigment-producing bacterium, but here we identify and characterize the production of a previously unreported colorful compound generated when cultured in a chemically defined medium. This finding reveals an underexplored aspect of <i>S. pyogenes</i> biology and raises the question of its contribution to pathogenesis. Given the established roles of microbial pigments in virulence and immune modulation in other pathogens, this work provides a foundation for future investigations into its functional significance and potential as a target for therapeutic or vaccine development.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0134826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025184","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":"Establishment of an <i>ex vivo</i> vascular tissue model to investigate bunyavirus-triggered vascular endothelial injury.","authors":"Zihan Guan, Xi Chen, Yujie Fang, Xiangtao Zhu, Shufen Li, Ke Peng","doi":"10.1128/mbio.01933-26","DOIUrl":"10.1128/mbio.01933-26","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome, an emerging infectious disease caused by the tick-borne bunyavirus severe fever with thrombocytopenia syndrome virus (SFTSV), is associated with a high clinical fatality rate of 12%-50%. Vascular endothelial injury triggered by SFTSV infection has been linked to severe disease progression and mortality. Currently, a suitable model to investigate the underlying mechanisms of SFTSV-induced vascular damage is lacking. Here, we show that the <i>ex vivo</i> human vascular tissue can be used as a model for studying bunyavirus-triggered endothelial injury. Both SFTSV and Rift Valley fever virus (RVFV) can successfully infect <i>ex vivo</i> human vascular tissue, as evidenced by detection of viral nucleoprotein and viral amplification in the tissue. Histopathological analysis, TUNEL staining, and endothelial injury-associated transcriptional changes revealed irregular venous tissue structure, luminal endothelial disruption, and apoptosis following infection. This model enables evaluation of antiviral compound efficacy, demonstrating that niclosamide or 4'-fluorouridine significantly inhibits SFTSV and RVFV replication in <i>ex vivo</i> vascular tissues. These findings establish the <i>ex vivo</i> human vascular tissue as a valuable tool for investigating bunyavirus-induced vascular pathogenesis and for evaluating antiviral therapeutics.</p><p><strong>Importance: </strong>Severe fever with thrombocytopenia syndrome virus and other pathogenic bunyaviruses cause severe human diseases that are frequently associated with vascular dysfunction. However, the mechanisms underlying virus-induced vascular injury remain poorly defined due to the lack of physiologically relevant human tissue models. Here, we establish an <i>ex vivo</i> human vascular tissue model that supports productive bunyavirus infection and enables quantitative assessment of endothelial injury, tissue damage, and antiviral efficacy. Using this model, we demonstrate that bunyavirus infection triggers endothelial disruption and that antiviral compounds can suppress viral replication and alleviate infection-associated tissue injury. This model provides a valuable experimental system for studying virus-vascular interactions and can support antiviral development against emerging bunyaviruses.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0193326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149039589","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}