mBio最新文献

{"title":"Retraction for Hiramatsu et al., \"The Mechanism of Pertussis Cough Revealed by the Mouse-Coughing Model\".","authors":"Yukihiro Hiramatsu, Koichiro Suzuki, Takashi Nishida, Naoki Onoda, Takashi Satoh, Shizuo Akira, Masahito Ikawa, Hiroko Ikeda, Junzo Kamei, Sandra Derouiche, Makoto Tominaga, Yasuhiko Horiguchi","doi":"10.1128/mbio.03921-24","DOIUrl":"10.1128/mbio.03921-24","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0392124"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A flagella-dependent <i>Burkholderia</i> jumbo phage controls rice seedling rot and steers <i>Burkholderia glumae</i> toward reduced virulence in rice seedlings.","authors":"Brittany S I Supina, Jaclyn G McCutcheon, Sydney R Peskett, Paul Stothard, Jonathan J Dennis","doi":"10.1128/mbio.02814-24","DOIUrl":"10.1128/mbio.02814-24","url":null,"abstract":"<p><p>Bacteriophages (phages) are being investigated as potential biocontrol agents for the suppression of bacterial diseases in cultivated crops. Jumbo bacteriophages, which possess genomic DNA larger than 200 kbp, generally have a broader host range than other phages and therefore would be useful as biocontrol agents against a wide range of bacterial strains. Thus, the characterization of novel jumbo phages specific for agricultural pathogens would be of importance for the development of phage biocontrol strategies. Herein, we demonstrate that phage S13 requires <i>Burkholderia glumae</i> flagella for its attachment and infection and that loss of <i>B. glumae</i> flagella prevents S13 cellular lysis. As flagella is a known virulence factor, loss of flagella results in a surviving population of <i>B. glumae</i> with reduced virulence. Further experimentation demonstrates that phage S13 can protect rice plants from <i>B. glumae</i>-sponsored destruction in a rice seedling model of infection.IMPORTANCEBacterial plant pathogens threaten many major food crops and inflict large agricultural losses worldwide. <i>B. glumae</i> is a bacterial plant pathogen that causes diseases such as rot, wilt, and blight in several food major crops including rice, tomato, hot pepper, and eggplant. <i>B. glumae</i> infects rice during all developmental stages, causing diseases such as rice seedling rot and bacterial panicle blight (BPB). The <i>B. glumae</i> incidence of rice plant infection is predicted to increase with warming global temperatures, and several different control strategies targeting <i>B. glumae</i> are being explored. These include chemical and antibiotic soil amendment, microbiome manipulation, and the use of partially resistant rice cultivars. However, despite rice growth amelioration, the treatment options for <i>B. glumae</i> plant infections remain limited to cultural practices. Alternatively, phage biocontrol represents a promising new method for eliminating <i>B. glumae</i> from crop soils and improving rice yields.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0281424"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bat adaptations in inflammation and cell death regulation contribute to viral tolerance.","authors":"Subham Das, Disha Jain, Priyansh Chaudhary, Rita M Quintela-Tizon, Arinjay Banerjee, Sannula Kesavardhana","doi":"10.1128/mbio.03204-23","DOIUrl":"10.1128/mbio.03204-23","url":null,"abstract":"<p><p>Bats are reservoirs for multiple viruses, some of which are known to cause global disease outbreaks. Virus spillovers from bats have been implicated in zoonotic transmission. Some bat species can tolerate viral infections, such as infections with coronaviruses and paramyxoviruses, better than humans and with less clinical consequences. Bat species are speculated to have evolved alongside these viral pathogens, and adaptations within the bat immune system are considered to be associated with viral tolerance. Inflammation and cell death in response to zoonotic virus infections prime human immunopathology. Unlike humans, bats have evolved adaptations to mitigate virus infection-induced inflammation. Inflammatory cell death pathways such as necroptosis and pyroptosis are associated with immunopathology during virus infections, but their regulation in bats remains understudied. This review focuses on the regulation of inflammation and cell death pathways in bats. We also provide a perspective on the possible contribution of cell death-regulating proteins, such as caspases and gasdermins, in modulating tissue damage and inflammation in bats. Understanding the role of these adaptations in bat immune responses can provide valuable insights for managing future disease outbreaks, addressing human disease severity, and improving pandemic preparedness.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0320423"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum for Betancourt et al., \"Pulmonary granuloma formation during latent <i>Cryptococcus neoformans</i> infection in C3HeB/FeJ mice involves progression through three immunological phases\".","authors":"Jovany J Betancourt, Minna Ding, J Marina Yoder, Issa Mutyaba, Hannah M Atkins, Gabriela De la Cruz, David B Meya, Kirsten Nielsen","doi":"10.1128/mbio.00595-25","DOIUrl":"https://doi.org/10.1128/mbio.00595-25","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0059525"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605453","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 Story behind the Science: Shining a light on the path to discovery.","authors":"Arturo Casadevall, Lorraine F Clark","doi":"10.1128/mbio.03679-24","DOIUrl":"10.1128/mbio.03679-24","url":null,"abstract":"","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0367924"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The high-osmolarity glycerol (HOG) pathway in <i>Candida auris</i>.","authors":"Hajar Yaakoub, Vincent Courdavault, Nicolas Papon","doi":"10.1128/mbio.03538-24","DOIUrl":"10.1128/mbio.03538-24","url":null,"abstract":"<p><p>The emerging fungal pathogen <i>Candida auris</i> is known for its strong skin tropism and resilience against antifungal and disinfection treatment, posing a significant challenge for healthcare units. Although efforts to identify the effectors of its unique pathogenic behavior have been insightful, the role of the high-osmolarity glycerol (HOG) pathway in this context remains unexplored. The study by Shivarathri and co-workers (R. Shivarathri, M. Chauhan, A. Datta, D. Das et al., mBio 15:e02748-24, 2024, https://doi.org/10.1128/mbio.02748-24) sought to address this gap. This report indeed advances our understanding of the critical role of the HOG pathway in <i>C. auris</i> pathogenicity by emphasizing its involvement in skin colonization, biofilm formation, and evasion of phagocyte attack.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0353824"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Control of <i>Clostridioides difficile</i> virulence and physiology by the flagellin homeostasis checkpoint FliC-FliW-CsrA in the absence of motility.","authors":"Duolong Zhu, Katherine J Wozniak, Firas Midani, Shaohui Wang, Xingmin Sun, Robert A Britton","doi":"10.1128/mbio.03801-24","DOIUrl":"10.1128/mbio.03801-24","url":null,"abstract":"<p><p>Mutations affecting <i>Clostridioides difficile</i> flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving <i>fliC</i>, <i>fliW</i>, and <i>csrA</i>, which creates a feedback system to regulate flagella production. Through genomic analysis of <i>C. difficile</i> clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene <i>fliC</i> and regulatory gene <i>fliW</i>. We therefore investigated the roles of <i>fliC</i>, <i>fliW</i>, and <i>csrA</i> in the clade 5 ribotype 078 strain <i>C. difficile</i> 1015, which lacks flagella and is non-motile. Analysis of mutations in <i>fliC</i>, <i>fliW</i>, and <i>csrA</i> (and all combinations) on <i>C. difficile</i> pathogenesis indicated that FliW plays a central role in <i>C. difficile</i> virulence as animals infected with strains carrying a deletion of <i>fliW</i> showed decreased survival and increased disease severity. These <i>in vivo</i> findings were supported by <i>in vitro</i> studies showing that mutations impacting the activity of FliW showed increased toxin production. We further identified that FliW can interact with the toxin-positive regulator TcdR, indicating that modulation of toxin production via FliW occurs by sequestering TcdR from activating toxin transcription. Furthermore, disruption of the <i>fliC-fliW-csrA</i> network results in significant changes in carbon source utilization and sporulation. This work highlights that key proteins involved in flagellar biosynthesis retain their regulatory roles in <i>C. difficile</i> pathogenesis and physiology independent of their functions in motility.</p><p><strong>Importance: </strong><i>Clostridioides difficile</i> is a leading cause of nosocomial antibiotic-associated diarrhea in developed countries with many known virulence factors. In several pathogens, motility and virulence are intimately linked by regulatory networks that allow coordination of these processes in pathogenesis and physiology. Regulation of <i>C. difficile</i> toxin production by FliC has been demonstrated <i>in vitro</i> and <i>in vivo</i> and has been proposed to link motility and virulence. Here, we show that clinically important, non-motile <i>C. difficile</i> strains have conserved FliC and regulatory partners FliW and CsrA, despite lacking the rest of the machinery to produce functional flagella. Our work highlights a novel role for flagellin outside of its role in motility and FliW in the pathogenesis and physiology of <i>C. difficile</i>.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0380124"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota does not influence tumor development in two models of heritable cancer.","authors":"Jessica Spring, Sandeep Gurbuxani, Tatyana Golovkina","doi":"10.1128/mbio.03866-24","DOIUrl":"10.1128/mbio.03866-24","url":null,"abstract":"<p><p>Microbial impact on tumorigenesis of heritable cancers proximal to the gut is well-documented. Whether the microbiota influences cancers arising from inborn mutations at sites distal to the gut is undetermined. Using two models of heritable cancer, <i>Trp53</i>-deficient mice and Wnt1-transgenic mice, and a gnotobiotic approach, we found the microbiota to be inconsequential for tumor development. This work furthers our understanding of the degree of the microbial impact on tumor development.</p><p><strong>Importance: </strong>The influence of the microbiome on the development of cancer is well-documented with many if not all published studies reporting either a positive or a negative impact. None of the published studies, however, presented data on the influence of the microbiome on the development of heritable cancer. We find that the microbiota has no influence on cancer development in two models of spontaneous cancers driven by germline <i>Trp53</i> deficiency and constitutive Wnt1 signaling.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0386624"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conserved lipid-facing basic residues promote the insertion of the porin OmpC into the <i>E. coli</i> outer membrane.","authors":"Janine H Peterson, Lixinhao Yang, James C Gumbart, Harris D Bernstein","doi":"10.1128/mbio.03319-24","DOIUrl":"10.1128/mbio.03319-24","url":null,"abstract":"<p><p>Almost all integral membrane proteins that reside in the outer membrane (OM) of gram-negative bacteria contain a closed amphipathic β sheet (\"β barrel\") that serves as a membrane anchor. The membrane integration of β barrel structures is catalyzed by a highly conserved heterooligomer called the <u>b</u>arrel <u>a</u>ssembly <u>m</u>achine (BAM). Although charged residues that are exposed to the lipid bilayer are infrequently found in outer membrane protein β barrels, the β barrels of OmpC/OmpF-type trimeric porins produced by Enterobacterales contain multiple conserved lipid-facing basic residues located near the extracellular side of the OM. Here, we show that these residues are required for the efficient insertion of the <i>Escherichia coli</i> OmpC protein into the OM <i>in vivo</i>. We found that the mutation of multiple basic residues to glutamine or alanine slowed insertion and reduced insertion efficiency. Furthermore, molecular dynamics simulations provided evidence that the basic residues promote the formation of hydrogen bonds and salt bridges with lipopolysaccharide, a unique glycolipid located exclusively in the outer leaflet of the OM. Taken together, our results support a model in which hydrophilic interactions between OmpC and LPS help to anchor the protein in the OM when the local environment is perturbed by BAM during membrane insertion and suggest a surprising role for membrane lipids in the insertion reaction.IMPORTANCEThe assembly (folding and membrane insertion) of bacterial outer membrane proteins (OMPs) is an essential cellular process that is a potential target for novel antibiotics. A heterooligomer called the <u>b</u>arrel <u>a</u>ssembly <u>m</u>achine (BAM) plays a major role in catalyzing OMP assembly. Here, we show that a group of highly conserved lipid-facing basic residues in <i>Escherichia coli</i> OmpC, a member of a major family of abundant OMPs known as trimeric porins, is required for the efficient integration of the protein into the outer membrane (OM). Based on our work and previous studies, we propose that the basic residues form interactions with a unique OM lipid (lipopolysaccharide) that promotes the insertion reaction. Our results provide strong evidence that interactions between specific membrane lipids and at least a subset of OMPs are required to supplement the activity of BAM and facilitate the integration of the proteins into the membrane.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0331924"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLO co-opts host cell glycosphingolipids to access cholesterol-rich lipid rafts for enhanced pore formation and cytotoxicity.","authors":"Pooja Sanduja, Stefanie S Schmieder, Buket Baddal, Songhai Tian, Jorge J Velarde, Wayne I Lencer, Min Dong, Michael R Wessels","doi":"10.1128/mbio.03777-24","DOIUrl":"10.1128/mbio.03777-24","url":null,"abstract":"<p><p>Streptolysin O (SLO) is a virulence determinant of group A <i>Streptococcus</i> (<i>S. pyogenes</i>), the agent of streptococcal sore throat and severe invasive infections. SLO is a member of a family of bacterial pore-forming toxins known as cholesterol-dependent cytolysins, which require cell membrane cholesterol for pore formation. While cholesterol is essential for cytolytic activity, accumulating data suggest that cell surface glycans may also participate in the binding of SLO and other cholesterol-dependent cytolysins to host cells. Here, we find that unbiased CRISPR screens for host susceptibility factors for SLO cytotoxicity identified genes encoding enzymes involved in the earliest steps of glycosphingolipid (GSL) biosynthesis. Targeted knockouts of these genes conferred relative resistance to SLO cytotoxicity in two independent human cell lines. Inactivation of <i>ugcg</i>, which codes for UDP-glucose ceramide glucosyltransferase, the enzyme catalyzing the first glycosylation step in GSL biosynthesis, reduced the clustering of SLO on the cell surface. This result suggests that binding to GSLs serves to cluster SLO molecules at lipid rafts where both GSLs and cholesterol are abundant. SLO clustering and susceptibility to SLO cytotoxicity were restored by reconstituting the GSL content of <i>ugcg</i> knockout cells with ganglioside GM1, but susceptibility to SLO cytotoxicity was not restored by a GM1 variant that lacks an oligosaccharide head group required for SLO binding, nor by a variant with a \"kinked\" acyl chain that prevents efficient packing of the ganglioside ceramide moiety with cholesterol. Thus, SLO appears to co-opt cell surface glycosphingolipids to gain access to lipid rafts for increased efficiency of pore formation and cytotoxicity.</p><p><strong>Importance: </strong>Group A <i>Streptococcus</i> is a global public health concern as it causes streptococcal sore throat and less common but potentially life-threatening invasive infections. Invasive infections have been associated with bacterial strains that produce large amounts of a secreted toxin, streptolysin O (SLO), which belongs to a family of pore-forming toxins produced by a variety of bacterial species. This study reveals that SLO binds to a class of molecules known as glycosphingolipids on the surface of human cells and that this interaction promotes efficient binding of SLO to cholesterol in the cell membrane and enhances pore formation. Understanding how SLO damages human cells provides new insight into streptococcal infection and may inform new approaches to treatment and prevention.</p>","PeriodicalId":18315,"journal":{"name":"mBio","volume":" ","pages":"e0377724"},"PeriodicalIF":5.1,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}