mBio最新文献

{"title":"Correction for Grünebast et al., \"Degradation of ribosomal RNA during <i>Plasmodium falciparum</i> gametocytogenesis\".","authors":"Janne Grünebast, Ritwik Singhal, Robin Bromley, Sachie Kanatani, Kaylee Watson, Sophie Olson, Franck Dumetz, Tales Vicari Pascini, Abhai Tripathi, Julie C Dunning Hotopp, Photini Sinnis, Manuel Llinás, David Serre","doi":"10.1128/mbio.01098-26","DOIUrl":"10.1128/mbio.01098-26","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0109826"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891714","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":"<i>Shewanella oneidensis</i> employs both β-lactam resistance and tolerance controlled by the PghKR system.","authors":"Jingxiao Cai, Yanqun Liang, Yu Chen, Xinyu Weng, Yiwei Hu, Min Wang, Qiu Meng, Zhiliang Yu, Jianhua Yin","doi":"10.1128/mbio.01515-26","DOIUrl":"10.1128/mbio.01515-26","url":null,"abstract":"<p><p>Antibiotic tolerance enables bacterial survival during antibiotic exposure and can promote the evolution of resistance, thereby threatening therapeutic efficacy. However, the molecular mechanisms underlying tolerance and its relationship with resistance remain incompletely understood. In this study, we show that a class D β-lactamase-deficient strain of <i>Shewanella oneidensis</i> (∆<i>blaA</i>) is highly susceptible to β-lactams, but retains the ability to survive lethal antibiotic concentrations. Under β-lactam stress, ∆<i>blaA</i> cells form reversible spheroplasts that revert to rod-shaped morphology and resume growth upon antibiotic removal, confirming a tolerance phenotype. Genetic analysis revealed that this tolerance depends on the peptidoglycan damage-responsive two-component system PghKR, which positively regulates the marine sortase target protein SO2195. Mechanistically, SO2195 preserves cell envelope integrity, thereby preventing spheroplast swelling and lysis under cell wall stress. SO2195 homologs are widely distributed across multiple bacterial classes and are consistently located adjacent to a sortase gene, suggesting a conserved functional module. The PghKR-mediated regulatory pathway also governs tolerance to other cell wall-acting antibiotics, such as D-cycloserine. Together with our previous findings that PghKR controls <i>blaA</i>-mediated β-lactam resistance, these results establish PghKR as a central regulatory hub that coordinately controls both resistance and tolerance, allowing bacteria to dynamically balance distinct survival strategies under bactericidal antibiotic stress.IMPORTANCEAntibiotic treatment failure is attributed not only to resistance, where bacteria grow in the presence of drugs, but also to tolerance, defined as the ability to survive bactericidal antibiotics without a change in minimum inhibitory concentration (MIC) and to resume growth upon drug removal. Whether a single bacterial population can concurrently employ and coordinate both strategies remains unclear. Such a scenario could challenge widely used combination therapies, such as those combining β-lactams with β-lactamase inhibitors. Here, using the intrinsically β-lactam-resistant bacterium <i>Shewanella oneidensis</i>, we show that bacteria can indeed employ both resistance and tolerance, and that both are controlled by a single regulatory system. Remarkably, even when primary β-lactamase-mediated resistance is abolished by genetic deletion, a dedicated tolerance pathway sustains bacterial survival. These findings reveal an integrated bacterial defense strategy and highlight the need to target both resistance and tolerance to overcome antibiotic treatment failure.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0151526"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963291","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":"Bacteria synthesize a bacteriocin within the cell membrane.","authors":"Fauzia H Nur, Ama N Antwi, Seth W Dickey","doi":"10.1128/mbio.01423-26","DOIUrl":"10.1128/mbio.01423-26","url":null,"abstract":"<p><p>Bacteria use bacteriocins to kill competitors and shape microbial communities. Many bacteriocins are ribosomally synthesized and post-translationally modified peptides (RiPPs), a diverse class of natural products and a source of new antimicrobials. The diversity of bacterial RiPPs stems from the combination of genetically encoded precursor peptides and biosynthetic proteins that post-translationally process the peptides. Characterized RiPP pathways involve soluble precursor peptides and biosynthetic proteins that modify them in the bacterial cytoplasm before secretion across the cell membrane. TMcins, a recently discovered RiPP class, challenge this paradigm by possessing a transmembrane helix in the mature product, indicating that bacteria have evolved a membrane-localized bacteriocin synthesis pathway. Here, we show that the precursor peptide TmcA is integrated into the producing cell membrane and, using an inducible TMcin biosynthesis system guided by structure prediction, is modified within the membrane, with three of four biosynthetic events mediated by intramembrane proteins. Notably, this approach revealed that a previously uncharacterized membrane protein performed an essential escort role during TMcin maturation within the cell membrane. Together, our findings reveal a membrane-localized pathway of RiPP biosynthesis, provide insights into its evolution, and establish TMcins as a model for understanding how bacteria produce peptide natural products from within the cell membrane.</p><p><strong>Importance: </strong>Bacteria have evolved numerous and diverse pathways to produce and secrete bacteriocins as weapons of bacterial warfare. These molecules are processed inside the cell and then transported across the bacterial membrane for secretion. We recently discovered the TMcins, a distinct class of bacteriocins found across gram-positive bacteria that contain a transmembrane helix and kill target bacteria by forming large pores. Using a <i>Staphylococcus aureus</i> strain that naturally produces TMcin, we show that TMcin production occurs in the cell membrane and reveal how bacteria process a membrane-spanning peptide in a lipid environment. This work expands our understanding of how bacteria produce antimicrobials and provides a model for discovering other membrane-localized natural products.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0142326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920134","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":"Fungal-bacterial interactions in the respiratory tract: from microbial interplay to clinical implications.","authors":"Lindsay G Pauls, Matheus Mertz Ribeiro, Gustavo H Goldman, Stephen K Dolan","doi":"10.1128/mbio.02330-25","DOIUrl":"10.1128/mbio.02330-25","url":null,"abstract":"<p><p>The respiratory tract harbors complex, dynamic microbial communities during infection, including bacteria (e.g., <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i>), fungi (e.g., <i>Aspergillus fumigatus</i> and <i>Cryptococcus neoformans</i>), and the resident respiratory microbiota. Within this ecosystem, microbes engage in cooperative and competitive interactions shaped by nutrient availability, immune modulation, and interkingdom chemical signaling, collectively influencing microbial persistence and pathogenic potential. While traditional studies have largely focused on single-pathogen infections, emerging evidence highlights the role of polymicrobial interactions-both synergistic and antagonistic-between pathogens and the respiratory microbiota in shaping disease progression in respiratory disorders. This minireview summarizes recent advances in understanding these complex microbial interactions and highlights key knowledge gaps and future directions in this rapidly evolving field.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0233025"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969821","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":"Neuropilin-1 is involved in lytic replication in a subset of primary effusion lymphoma cell lines and for KSHV gene expression in primary endothelial cells.","authors":"Anna K P Serquina, Julie Lee, Eric Cho, Guruswamy Mahesh, Bahman Afsari, Joseph M Ziegelbauer","doi":"10.1128/mbio.01001-26","DOIUrl":"10.1128/mbio.01001-26","url":null,"abstract":"<p><p>Primary effusion lymphoma (PEL) is a B cell lymphoma that occurs most often in people living with HIV/AIDS and is caused by Kaposi sarcoma herpesvirus (KSHV). Most are also infected with Epstein-Barr virus (EBV). While newer regimens now exist, PEL still has poorer outcomes compared to other HIV-associated lymphomas. Since PEL B cells lack typical B cell markers, we aim to identify other surface proteins in disease cells that may act as possible diagnostic or prognostic markers. We performed single cell DNA-seq and antibody derived tag-seq on BCBL1 (KSHV+/EBV-) and LCL (KSHV-/EBV+ lymphoblastoid cell line) cells to determine which surface markers are specific for KSHV+ PEL. We identified neuropilin-1 (NRP1) as a surface marker that is overexpressed in KSHV+ PEL cell lines (BCBL1, JSC1), but not in EBV+ LCL cells. NRP1 depletion during reactivation reduced lytic transcription, virion production, and infectivity of NRP1+ PEL cell lines. Selected NRP1+ PEL cells also expressed higher levels of <i>NANOG</i> and <i>OCT3/4</i> compared to controls. NRP1+ PEL cells had higher amounts of lytic transcripts. Conversely, lytic cells express higher amounts of NRP1 transcripts at the single-cell level. Overexpression of NRP1 resulted in significantly higher lytic transcripts during lytic induction. Our findings suggest that NRP1 is a surface marker expressed for a subtype of PEL cells that is required for efficient lytic replication. It is also associated with increased expression of stemness markers, denoting poor prognosis in cancer.IMPORTANCEKSHV is a cancer-causing herpesvirus that is the etiologic agent for primary effusion lymphoma (PEL), with half of patients who are chemotherapy-resistant and have poor prognosis overall. Here, we present our discovery of NRP1 as a surface marker for a proposed subtype of PEL cell lines. We present data that support a role for NRP1 in generating infectious progeny virions and that NRP1 is associated with viral gene expression during its lytic phase. Due to NRP1's role in cancer as studied by others, it is possible that NRP1 is contributing toward worse clinical outcomes in a subgroup of people with PEL. We propose that NRP1 is a potential prognostic marker for a certain category of PEL and can be targeted in chemotherapy-resistant PEL since small molecule inhibitors against NRP1 are already available.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0100126"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969924","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 molecular safeguard in <i>Escherichia coli</i> Braun's lipoprotein (Lpp) biogenesis.","authors":"Emily J LaMarre, Makayla R Braunlin, Brian Kloss, Faiza Rafi, Bogdan I Iorga, Anuradha Janakiraman","doi":"10.1128/mbio.01845-26","DOIUrl":"10.1128/mbio.01845-26","url":null,"abstract":"<p><p>Braun's lipoprotein (Lpp) is the most abundant protein present in <i>Escherichia coli</i>. Lpp is an outer membrane (OM) lipoprotein that contributes to the mechanical integrity of the cell envelope by tethering the OM to the underlying peptidoglycan (PGN). It has long been known that Lpp accumulation at the inner membrane (IM) is toxic due to aberrant tethering of the IM to the PGN. However, it is not known if there exists a cellular mechanism that mitigates such anomalous Lpp-mediated linkages. Here, we report the identification of DcrB, an inner membrane lipoprotein, as a molecular safeguard of Lpp biogenesis in <i>E. coli</i>. We demonstrate that DcrB promotes <i>E. coli</i> viability under conditions of lipoprotein maturation stress, and that in its absence Lpp-PGN linkages are altered. Genetic and biochemical tests reveal that DcrB's function is in promoting the efficiency of Lpp maturation, likely through a direct interaction. Overall, our results are consistent with two, albeit not mutually exclusive, roles for DcrB in Lpp biogenesis: promoting Lpp maturation and ameliorating the formation of deleterious IM-Lpp-PGN linkages.IMPORTANCELpp, an outer membrane (OM) lipoprotein, was discovered more than five decades ago as the first member of the bacterial lipoprotein family, which constitutes a group of important cell envelope proteins. Lpp crosslinks the OM to the underlying peptidoglycan (PGN) and contributes to the structural integrity of the cell envelope. However, Lpp-mediated crosslinks from the inner membrane (IM) to the PGN are toxic. Here, we identify an IM lipoprotein, DcrB, that binds Lpp and improves the efficiency of Lpp's journey across the IM. In so doing, DcrB attenuates the formation of aberrant IM-PGN linkages. Overall, this study reveals the existence of a critical safeguard in the biogenesis of Lpp, a paradigmatic bacterial lipoprotein.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0184526"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990436","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":"Yersinopine is a primary zinc acquisition system for <i>Yersinia pseudotuberculosis</i>.","authors":"Mahendar Kadari, Casey Weber, Thomas E Kehl-Fie, Robert D Perry, Juan C Ortiz-Marquez, Oleg V Tsodikov, Sylvie Garneau-Tsodikova, Matthew B Lawrenz","doi":"10.1128/mbio.02000-26","DOIUrl":"10.1128/mbio.02000-26","url":null,"abstract":"<p><p>Y<i>ersinia pestis</i> is a vector-borne pathogen that evolved from the enteric pathogen <i>Yersinia pseudotuberculosis</i>. Despite different routes of infection, both pathogens need to overcome host-mediated zinc limitation. <i>Y. pestis</i> relies on the transporter ZnuABC and the metallophore yersiniabactin, but surprisingly, disruption of these systems in <i>Y. pseudotuberculosis</i> did not limit growth during zinc limitation, suggesting the presence of additional mechanisms. Here, we identify the opine-type metallophore yersinopine, encoded by the <i>cnt</i> operon, as a primary zinc uptake system in <i>Y. pseudotuberculosis</i>. While a <i>znuA ybtX</i> mutant was not attenuated for growth in metal-limited medium, <i>cnt znuA</i> and <i>cnt ybtX</i> mutants both had significant growth defects. Moreover, a <i>znuA ybtX cnt</i> mutant was completely attenuated for growth, which was rescued by zinc but not iron supplementation. While the <i>cnt</i> operon is present in <i>Y. pestis</i>, growth of analogous <i>cnt</i> mutants was not altered. Comparison of the <i>cnt</i> operons indicated the presence of two frameshift mutations in the predicted yersinopine importer <i>cntQ</i> in <i>Y. pestis</i>, suggesting that it is a pseudogene. Indeed, introduction of the same mutations into <i>cntQ</i> in <i>Y. pseudotuberculosis znuA ybtX</i> phenocopied a <i>znuA ybtX cnt</i> mutant. Finally, yersinopine also contributed to <i>Y. pseudotuberculosis</i> fitness in the presence of calprotectin and during infection in the murine model of yersiniosis. These data establish yersinopine as a primary zinc acquisition system in <i>Y. pseudotuberculosis</i> that is not required for <i>Y. pestis</i> to overcome zinc-mediated nutritional immunity and show divergent evolution in zinc acquisition strategies in these closely related species.<b>IMPORTANCE</b>Zinc sequestration by the host is a major component of nutritional immunity that restricts bacterial growth during infection. Here, we identify the opine metallophore yersinopine as a primary zinc acquisition system in <i>Yersinia pseudotuberculosis</i>. Yersinopine promotes fitness during calprotectin-mediated zinc starvation and contributes to virulence during infection. In contrast, yersinopine does not support zinc uptake in <i>Yersinia pestis</i> due to inactivating mutations in the protein required for uptake of zinc-bound yersinopine. These findings establish yersinopine-dependent zinc acquisition as a critical virulence factor in <i>Y. pseudotuberculosis</i> and reveal a previously unrecognized evolutionary divergence in metal acquisition strategies among closely related <i>Yersinia</i> species.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0200026"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148990540","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":"Pan-proteome regulation of marine <i>Synechococcus</i> nutrient stress plasticity.","authors":"Nathan S Garcia, Mak A Saito, Renne Harcourt, Matthew R McIlvin, Adam C Martiny","doi":"10.1128/mbio.02247-26","DOIUrl":"https://doi.org/10.1128/mbio.02247-26","url":null,"abstract":"<p><p>Variable phytoplankton resource demands can buffer productivity to climate-driven declines in nutrient supply, but the extent of this buffering depends on limits to cellular elemental plasticity. Elemental plasticity is driven by a combination of genomic adaptation and physiological regulation, but their mechanistic links remain unresolved. Here, we combine continuous culture experiments with proteomics and elemental analyses to determine how genomic diversity shapes nutrient stress plasticity in six strains of the globally distributed cyanobacterium <i>Synechococcus</i>. By maintaining fixed growth rates in chemostats under nitrogen- or phosphorus-limiting conditions, we disentangle lineage-specific resource demands from growth effects. All strains show conserved induction of nutrient acquisition pathways, yet strain identity explains most pan-proteome variance, and variation in non-core protein expression predicts deviations in elemental plasticity. Strains from oligotrophic compared to mesotrophic regions exhibit broader proteomic adjustments and wider C:P and N:P ranges. Our findings show that genomic diversity expressed through pan-proteome regulation amplifies physiological plasticity and increases phytoplankton nutrient stress buffering capacity under future climate conditions.IMPORTANCEMarine cyanobacteria are among the most abundant microbes on Earth and play central roles in global nutrient cycling, yet the molecular mechanisms that determine how they respond to nutrient stress remain poorly understood. Here, we show that genomic diversity within the marine cyanobacterium <i>Synechococcus</i> translates into differences in protein expression and cellular resource allocation. Combining chemostat experiments and proteomics across multiple strains, we demonstrate that variation in the non-core genome shapes how lineages regulate nutrient acquisition pathways and adjust cellular C:N:P stoichiometry under nitrogen or phosphorus stress. These results reveal how pan-genome diversity generates physiological plasticity within microbial populations, providing a mechanistic link between microbial genomic variation and ecosystem-level nutrient cycling in the ocean.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0224726"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182910","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":"Dynamic and distinct physiological responses by a soil bacterium promote survival along a desiccation continuum.","authors":"Jarek V Kwiecinski, Georgia R Squyres, Dani Or, Dianne K Newman","doi":"10.1128/mbio.01903-26","DOIUrl":"10.1128/mbio.01903-26","url":null,"abstract":"<p><p>Soil bacteria play a central role in global biogeochemical cycles and are critical for soil health and agricultural productivity. The dynamic nature of soil hydration status affects bacterial habitats by changing the energy state of soil water and disrupting aqueous connections critical for nutrient diffusion. To study how soil bacteria respond to desiccation, we used the rhizobacterium <i>Pseudomonas synxantha</i> 2-79 as a model organism and quantified its response to co-occurring water and nutrient limitations at the single-cell level. We hypothesized that the relative importance of osmolyte synthesis and starvation responses to desiccation tolerance is context dependent, with the optimal strategy determined by the trajectory of nutrient and water deprivation. We constructed a transcriptional reporter to track <i>P. synxantha</i>'s expression of biosynthesis genes for the osmolyte N-acetylglutaminylglutamine amide (NAGGN) and collected extensive single-cell growth rate, cell size, and reporter expression data through experiments that mimicked different rates and extents of soil drying. Only actively growing cells responded to an osmotic shock by synthesizing NAGGN; this response was not observed for pre-starved bacteria. Despite the lack of osmolyte NAGGN synthesis, prior starvation enhanced <i>P. synxantha'</i>s ability to recover from osmotic stress once water and nutrients were restored. In line with our observation that prior starvation prevented cell lysis upon rewetting, starved cells had more rigid membranes. Together, our results indicate that diverse cellular properties contribute to soil bacterial desiccation tolerance, whose relative response and fitness are tuned to different challenges imposed by soil drying dynamics.IMPORTANCESoil bacteria are critical to agriculture, but it is unclear how these organisms respond to desiccation, a common and worsening stress. Desiccation both dehydrates bacterial cells and eliminates the liquid water connections between soil pores that bacteria use to access nutrients. We studied how a model soil bacterium responds to (co)-occurring starvation and water stress at the single-cell level, focusing on osmolyte synthesis and physiological adjustments that take place under starvation. We describe the desiccation and regrowth trajectories in these conditions at single-cell resolution. We find that starvation restricts synthesis of a dipeptide osmolyte but rigidifies the membrane, enabling bacteria to withstand more severe water stress. Distinct cellular factors thus contribute differentially to desiccation tolerance along a drying trajectory.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0190326"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865652","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 uniquely human sebum lipid drives streptococcal skin infection severity.","authors":"Doris L LaRock, Christopher N LaRock","doi":"10.1128/mbio.01856-26","DOIUrl":"10.1128/mbio.01856-26","url":null,"abstract":"<p><p>Free fatty acids (FAs) secreted by the sebaceous glands are critical components of the skin barrier. Here, we investigate the activity of the major FA species present in the skin against <i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i> [GAS]), a major cause of skin infections, such as impetigo, erysipelas, cellulitis, and necrotizing fasciitis. Several relevant FAs had antimicrobial activity against GAS, and linoleic acid was found to be therapeutic when applied in a murine skin infection model. However, sapienic acid, a FA abundant only in human sebum, significantly worsened disease severity despite possessing antimicrobial activity. Transcriptional profiling and molecular genetic analysis showed that sapienic acid, but not other structurally similar FAs, induced the <i>sag</i> operon. The <i>sag</i> operon encodes streptolysin S (SLS), and sapienic acid induction of this cytolytic toxin significantly increased hemolysis of human red blood cells by GAS. Screening of additional FAs identified forms with combined antimicrobial and anti-lytic activity useful as therapeutics. Taken together, we report a species- and tissue-specific trigger for GAS virulence and limitations to the use of FAs as therapeutics against infectious disease.IMPORTANCEGAS naturally only infects humans. Here, we report that the human-specific sebum lipid sapienic acid induces production of streptolysin S (SLS), the hemolysin responsible for the hallmark β-hemolytic phenotype of GAS. Reliance on detection of a human-specific FA for expression of a critical virulence factor exposes a vulnerability of GAS and suggests a potentially variable role for SLS at different infection sites. Furthermore, it details a limitation of existing infection models, which all lack sapienic acid, for understanding the role of SLS in disease.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0185626"},"PeriodicalIF":5.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887789","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}