Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Department of Molecular Biology, School of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
Infect Immun. 2023 May 16;91(5):e0043522. doi: 10.1128/iai.00435-22. Epub 2023 Apr 6.
In order for successful fecal-oral transmission, enteric bacterial pathogens have to successfully compete with the intestinal microbiota and reach high concentrations during infection. Vibrio cholerae requires cholera toxin (CT) to cause diarrheal disease, which is thought to promote the fecal-oral transmission of the pathogen. Besides inducing diarrheal disease, the catalytic activity of CT also alters host intestinal metabolism, which promotes the growth of V. cholerae during infection through the acquisition of host-derived nutrients. Furthermore, recent studies have found that CT-induced disease activates a niche-specific suite of V. cholerae genes during infection, some of which may be important for fecal-oral transmission of the pathogen. Our group is currently exploring the concept that CT-induced disease promotes the fecal-oral transmission of V. cholerae by modulating both host and pathogen metabolism. Furthermore, the role of the intestinal microbiota in pathogen growth and transmission during toxin-induced disease merits further investigation. These studies open the door to investigating whether other bacterial toxins also enhance pathogen growth and transmission during infection, which may shed light on the design of novel therapeutics for intervention or prevention of diarrheal diseases.
为了实现成功的粪-口传播，肠道细菌病原体必须成功地与肠道微生物群竞争，并在感染期间达到高浓度。霍乱弧菌需要霍乱毒素 (CT) 才能引起腹泻病，这被认为有助于病原体的粪-口传播。除了诱导腹泻病外，CT 的催化活性还改变了宿主肠道代谢，通过获取宿主来源的营养物质促进感染期间霍乱弧菌的生长。此外，最近的研究发现，CT 诱导的疾病在感染过程中激活了霍乱弧菌特定生态位的一套基因，其中一些基因可能对病原体的粪-口传播很重要。我们的研究小组目前正在探索 CT 诱导的疾病通过调节宿主和病原体代谢来促进霍乱弧菌的粪-口传播的概念。此外，肠道微生物群在毒素诱导疾病期间对病原体生长和传播的作用值得进一步研究。这些研究为研究其他细菌毒素是否也能在感染过程中增强病原体的生长和传播开辟了道路，这可能为干预或预防腹泻病的新型治疗方法的设计提供了思路。
