Mark T Anderson, Stephanie D Himpsl, Leandra G Kingsley, Sara N Smith, Michael A Bachman, Harry L T Mobley
{"title":"Serratia marcescens 胶囊菌系的感染特征。","authors":"Mark T Anderson, Stephanie D Himpsl, Leandra G Kingsley, Sara N Smith, Michael A Bachman, Harry L T Mobley","doi":"10.1101/2024.08.23.609398","DOIUrl":null,"url":null,"abstract":"<p><p><i>Serratia marcescens</i> is a healthcare-associated pathogen that can cause severe infections including bacteremia and pneumonia. The capsule polysaccharide of <i>S. marcescens</i> is a bacteremia fitness determinant and previous work defined capsule locus (KL) diversity within the species. Strains belonging to KL1 and KL2 capsule clades produce sialylated polysaccharides and represent the largest subpopulation of isolates from clinical origin. In this study, the contribution of these and other <i>S. marcescens</i> capsules to infection was determined in animal and cellular models. Using a murine model of primary bacteremia, clinical isolates of multiple KL types demonstrated capsule-dependent colonization of spleen, liver, and kidney following tail vein inoculation. Similar results were observed using a bacteremic pneumonia model, in that all tested strains of clinical origin demonstrated a requirement for capsule in both the primary lung infection site and for bloodstream dissemination to secondary organs. Finally, capsule from each KL clade was examined for the ability to resist internalization by bone marrow-derived macrophages. Only the sialylated KL1 and KL2 clade strains exhibited capsule-dependent inhibition of internalization, including KL2 capsule produced in a heterologous background. Together these findings indicate that lineage-specific resistance to macrophage phagocytosis may enhance survival and antibacterial defenses of clinically-adapted <i>S. marcescens</i>.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370568/pdf/","citationCount":"0","resultStr":"{\"title\":\"Infection characteristics among <i>Serratia marcescens</i> capsule lineages.\",\"authors\":\"Mark T Anderson, Stephanie D Himpsl, Leandra G Kingsley, Sara N Smith, Michael A Bachman, Harry L T Mobley\",\"doi\":\"10.1101/2024.08.23.609398\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Serratia marcescens</i> is a healthcare-associated pathogen that can cause severe infections including bacteremia and pneumonia. The capsule polysaccharide of <i>S. marcescens</i> is a bacteremia fitness determinant and previous work defined capsule locus (KL) diversity within the species. Strains belonging to KL1 and KL2 capsule clades produce sialylated polysaccharides and represent the largest subpopulation of isolates from clinical origin. In this study, the contribution of these and other <i>S. marcescens</i> capsules to infection was determined in animal and cellular models. Using a murine model of primary bacteremia, clinical isolates of multiple KL types demonstrated capsule-dependent colonization of spleen, liver, and kidney following tail vein inoculation. Similar results were observed using a bacteremic pneumonia model, in that all tested strains of clinical origin demonstrated a requirement for capsule in both the primary lung infection site and for bloodstream dissemination to secondary organs. Finally, capsule from each KL clade was examined for the ability to resist internalization by bone marrow-derived macrophages. Only the sialylated KL1 and KL2 clade strains exhibited capsule-dependent inhibition of internalization, including KL2 capsule produced in a heterologous background. Together these findings indicate that lineage-specific resistance to macrophage phagocytosis may enhance survival and antibacterial defenses of clinically-adapted <i>S. marcescens</i>.</p>\",\"PeriodicalId\":519960,\"journal\":{\"name\":\"bioRxiv : the preprint server for biology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-03-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370568/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"bioRxiv : the preprint server for biology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/2024.08.23.609398\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"bioRxiv : the preprint server for biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2024.08.23.609398","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
Serratia marcescens 是一种与医疗保健相关的病原体,可引起血流感染、肺炎和尿路感染。S. marcescens 的胶囊多糖在感染过程中是一个关键的适应性决定因素,最近的工作确定了该物种内胶囊基因座(KL)遗传序列之间的关系。属于 KL1 和 KL2 胶囊支系的菌株产生苷元化多糖,代表了临床来源分离物中最大的亚群,而 S. marcescens 型菌株和其他环境分离物被归类为 KL5。在这项工作中,我们确定了这些胶囊和其他胶囊在多种感染模型中对致病机理的贡献。利用小鼠尾静脉注射菌血症模型,临床菌株在接种后表现出脾脏、肝脏和肾脏的胶囊依赖性定植。相比之下,KL5 菌株在该模型中删除胶囊基因后存活率没有下降。此外,与 KL1 菌株相比,野生型 KL5 菌株从脾脏和肝脏中清除的速度更快。在菌血症性肺炎模型中也观察到了类似的结果,所有经过测试的临床来源菌株都表明,在肺部原发感染部位和血液传播到其他器官时都需要胶囊。最后,对每个 KL 支系的菌株进行了检测,以确定胶囊在骨髓巨噬细胞内化过程中的作用。只有代表大多数临床分离菌株的 KL1 和 KL2 支链菌株表现出依赖胶囊的内化抑制作用,这表明胶囊介导的巨噬细胞吞噬阻力可能会提高感染期间的存活率和抗菌防御能力:细菌血流感染源于宿主先天性免疫系统的逃避和最初来自内部或外部的接种事件后的稳定定植。囊多糖在菌血症期间对大肠埃希氏菌起到保护作用,但该物种内的囊编码基因座存在丰富的遗传多样性。本研究比较了属于五种不同胶囊类型的 S. marcescens 分离物的感染特征,并确定了每种类型对感染适应性的贡献。通过分析 S. marcescens 菌株对胶囊的依赖性和感染潜力的差异,可以将抗击这些威胁生命的感染的工作重点放在确定针对这种重要机会性病原体的最关键基因系的策略上。
Infection characteristics among Serratia marcescens capsule lineages.
Serratia marcescens is a healthcare-associated pathogen that can cause severe infections including bacteremia and pneumonia. The capsule polysaccharide of S. marcescens is a bacteremia fitness determinant and previous work defined capsule locus (KL) diversity within the species. Strains belonging to KL1 and KL2 capsule clades produce sialylated polysaccharides and represent the largest subpopulation of isolates from clinical origin. In this study, the contribution of these and other S. marcescens capsules to infection was determined in animal and cellular models. Using a murine model of primary bacteremia, clinical isolates of multiple KL types demonstrated capsule-dependent colonization of spleen, liver, and kidney following tail vein inoculation. Similar results were observed using a bacteremic pneumonia model, in that all tested strains of clinical origin demonstrated a requirement for capsule in both the primary lung infection site and for bloodstream dissemination to secondary organs. Finally, capsule from each KL clade was examined for the ability to resist internalization by bone marrow-derived macrophages. Only the sialylated KL1 and KL2 clade strains exhibited capsule-dependent inhibition of internalization, including KL2 capsule produced in a heterologous background. Together these findings indicate that lineage-specific resistance to macrophage phagocytosis may enhance survival and antibacterial defenses of clinically-adapted S. marcescens.