Qiwen Dong, Stephen Harper, Emma McSpadden, Sophie S. Son, Marie-Maude Allen, Huaiying Lin, Rita C. Smith, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Anitha Sundararajan, Amber Rose, Mary McMillin, David Moran, Jessica Little, Michael W. Mullowney, Ashley M. Sidebottom, Louis-Charles Fortier, Aimee Shen, Eric G. Pamer
{"title":"用天然无毒菌株预防艰难梭菌病","authors":"Qiwen Dong, Stephen Harper, Emma McSpadden, Sophie S. Son, Marie-Maude Allen, Huaiying Lin, Rita C. Smith, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Anitha Sundararajan, Amber Rose, Mary McMillin, David Moran, Jessica Little, Michael W. Mullowney, Ashley M. Sidebottom, Louis-Charles Fortier, Aimee Shen, Eric G. Pamer","doi":"10.1016/j.chom.2024.11.003","DOIUrl":null,"url":null,"abstract":"<em>Clostridioides difficile</em> is a leading cause of healthcare infections. Gut dysbiosis promotes <em>C. difficile</em> infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence. Although therapies preventing recurrent CDI have been developed, including live biotherapeutic products, existing therapies are costly and do not prevent primary infections. Here, we show that an avirulent <em>C. difficile</em> isolate, ST1-75, protects mice from developing colitis induced by a virulent R20291 strain when coinfected at a 1:1 ratio. In metabolic analyses, avirulent ST1-75 depletes amino acids more rapidly than virulent R20291 and supplementation with amino acids ablates this competitive advantage, indicating that ST1-75 limits the growth of virulent R20291 through amino acid depletion. Overall, our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI and reveals that the ST1-75 strain may be a biotherapeutic agent that can prevent CDI in high-risk patients.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"1 1","pages":""},"PeriodicalIF":20.6000,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protection against Clostridioides difficile disease by a naturally avirulent strain\",\"authors\":\"Qiwen Dong, Stephen Harper, Emma McSpadden, Sophie S. Son, Marie-Maude Allen, Huaiying Lin, Rita C. Smith, Carolyn Metcalfe, Victoria Burgo, Che Woodson, Anitha Sundararajan, Amber Rose, Mary McMillin, David Moran, Jessica Little, Michael W. Mullowney, Ashley M. Sidebottom, Louis-Charles Fortier, Aimee Shen, Eric G. Pamer\",\"doi\":\"10.1016/j.chom.2024.11.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<em>Clostridioides difficile</em> is a leading cause of healthcare infections. Gut dysbiosis promotes <em>C. difficile</em> infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence. Although therapies preventing recurrent CDI have been developed, including live biotherapeutic products, existing therapies are costly and do not prevent primary infections. Here, we show that an avirulent <em>C. difficile</em> isolate, ST1-75, protects mice from developing colitis induced by a virulent R20291 strain when coinfected at a 1:1 ratio. In metabolic analyses, avirulent ST1-75 depletes amino acids more rapidly than virulent R20291 and supplementation with amino acids ablates this competitive advantage, indicating that ST1-75 limits the growth of virulent R20291 through amino acid depletion. Overall, our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI and reveals that the ST1-75 strain may be a biotherapeutic agent that can prevent CDI in high-risk patients.\",\"PeriodicalId\":9693,\"journal\":{\"name\":\"Cell host & microbe\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":20.6000,\"publicationDate\":\"2024-11-27\",\"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.2024.11.003\",\"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.2024.11.003","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Protection against Clostridioides difficile disease by a naturally avirulent strain
Clostridioides difficile is a leading cause of healthcare infections. Gut dysbiosis promotes C. difficile infection (CDI) and CDIs promote gut dysbiosis, leading to frequent CDI recurrence. Although therapies preventing recurrent CDI have been developed, including live biotherapeutic products, existing therapies are costly and do not prevent primary infections. Here, we show that an avirulent C. difficile isolate, ST1-75, protects mice from developing colitis induced by a virulent R20291 strain when coinfected at a 1:1 ratio. In metabolic analyses, avirulent ST1-75 depletes amino acids more rapidly than virulent R20291 and supplementation with amino acids ablates this competitive advantage, indicating that ST1-75 limits the growth of virulent R20291 through amino acid depletion. Overall, our study identifies inter-strain nutrient depletion as a potentially exploitable mechanism to reduce the incidence of CDI and reveals that the ST1-75 strain may be a biotherapeutic agent that can prevent CDI in high-risk patients.
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.