Thomas E. Barton, Angharad E. Green, Kate C. Mellor, Abigail E. McKnight, Katharina Bacher, Sumit Kumar, Kyle Newbold, Oliver Lorenz, Elizabeth Pohler, Manal S. Monshi, Adam Bryson, Felix Dube, Heather J. Zar, Mark P. Nicol, Stephen D. Bentley, Markus Hilty, Jason W. Rosch, Stephanie Lo, Daniel R. Neill
{"title":"自然获得的启动子变异影响肺炎链球菌感染的结果","authors":"Thomas E. Barton, Angharad E. Green, Kate C. Mellor, Abigail E. McKnight, Katharina Bacher, Sumit Kumar, Kyle Newbold, Oliver Lorenz, Elizabeth Pohler, Manal S. Monshi, Adam Bryson, Felix Dube, Heather J. Zar, Mark P. Nicol, Stephen D. Bentley, Markus Hilty, Jason W. Rosch, Stephanie Lo, Daniel R. Neill","doi":"10.1016/j.chom.2025.08.005","DOIUrl":null,"url":null,"abstract":"<em>Streptococcus pneumoniae</em> colonizes human airways, where it acquires sugars from glycosylated mucins using glycoside hydrolases and sugar transport systems. This study identifies widespread nucleotide sequence variation in the promoter of a pneumococcal operon encoding a glycan scavenging system. We identify 78 promoter sequence patterns across 21,155 genomes, with variation clustered within a stretch of adenines, where mutations accumulate via strand slippage during DNA replication. Promoter mutations influence operon transcription, and multiple promoter patterns are co-identified during single-carriage episodes, suggesting that heterogeneous gene expression provides population-level benefits. In a mouse nasopharyngeal colonization model, promoter mutations arise and undergo selection, with nucleotide insertion promoting gene expression and prolonging carriage longevity. Pre-existing immunity confers resistance to colonization by strains carrying single promoter patterns but does not protect against mixed infections with otherwise isogenic strains differing in promoter sequence. Promoter region sequence variation offers an evolutionary strategy for exploration of phenotypic space to maximize fitness within-host.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"29 1","pages":""},"PeriodicalIF":18.7000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Naturally acquired promoter variation influences Streptococcus pneumoniae infection outcomes\",\"authors\":\"Thomas E. Barton, Angharad E. Green, Kate C. Mellor, Abigail E. McKnight, Katharina Bacher, Sumit Kumar, Kyle Newbold, Oliver Lorenz, Elizabeth Pohler, Manal S. Monshi, Adam Bryson, Felix Dube, Heather J. Zar, Mark P. Nicol, Stephen D. Bentley, Markus Hilty, Jason W. Rosch, Stephanie Lo, Daniel R. Neill\",\"doi\":\"10.1016/j.chom.2025.08.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<em>Streptococcus pneumoniae</em> colonizes human airways, where it acquires sugars from glycosylated mucins using glycoside hydrolases and sugar transport systems. This study identifies widespread nucleotide sequence variation in the promoter of a pneumococcal operon encoding a glycan scavenging system. We identify 78 promoter sequence patterns across 21,155 genomes, with variation clustered within a stretch of adenines, where mutations accumulate via strand slippage during DNA replication. Promoter mutations influence operon transcription, and multiple promoter patterns are co-identified during single-carriage episodes, suggesting that heterogeneous gene expression provides population-level benefits. In a mouse nasopharyngeal colonization model, promoter mutations arise and undergo selection, with nucleotide insertion promoting gene expression and prolonging carriage longevity. Pre-existing immunity confers resistance to colonization by strains carrying single promoter patterns but does not protect against mixed infections with otherwise isogenic strains differing in promoter sequence. Promoter region sequence variation offers an evolutionary strategy for exploration of phenotypic space to maximize fitness within-host.\",\"PeriodicalId\":9693,\"journal\":{\"name\":\"Cell host & microbe\",\"volume\":\"29 1\",\"pages\":\"\"},\"PeriodicalIF\":18.7000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell host & microbe\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.chom.2025.08.005\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell host & microbe","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.chom.2025.08.005","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Streptococcus pneumoniae colonizes human airways, where it acquires sugars from glycosylated mucins using glycoside hydrolases and sugar transport systems. This study identifies widespread nucleotide sequence variation in the promoter of a pneumococcal operon encoding a glycan scavenging system. We identify 78 promoter sequence patterns across 21,155 genomes, with variation clustered within a stretch of adenines, where mutations accumulate via strand slippage during DNA replication. Promoter mutations influence operon transcription, and multiple promoter patterns are co-identified during single-carriage episodes, suggesting that heterogeneous gene expression provides population-level benefits. In a mouse nasopharyngeal colonization model, promoter mutations arise and undergo selection, with nucleotide insertion promoting gene expression and prolonging carriage longevity. Pre-existing immunity confers resistance to colonization by strains carrying single promoter patterns but does not protect against mixed infections with otherwise isogenic strains differing in promoter sequence. Promoter region sequence variation offers an evolutionary strategy for exploration of phenotypic space to maximize fitness within-host.
期刊介绍:
Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.