Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
PLoS One. 2010 Jan 15;5(1):e8740. doi: 10.1371/journal.pone.0008740.
Clostridium difficile, a spore-forming bacterium, causes antibiotic-associated diarrhea. In order to produce toxins and cause disease, C. difficile spores must germinate and grow out as vegetative cells in the host. Although a few compounds capable of germinating C. difficile spores in vitro have been identified, the in vivo signal(s) to which the spores respond were not previously known. Examination of intestinal and cecal extracts from untreated and antibiotic-treated mice revealed that extracts from the antibiotic-treated mice can stimulate colony formation from spores to greater levels. Treatment of these extracts with cholestyramine, a bile salt binding resin, severely decreased the ability of the extracts to stimulate colony formation from spores. This result, along with the facts that the germination factor is small, heat-stable, and water-soluble, support the idea that bile salts stimulate germination of C. difficile spores in vivo. All extracts able to stimulate high level of colony formation from spores had a higher proportion of primary to secondary bile salts than extracts that could not. In addition, cecal flora from antibiotic-treated mice was less able to modify the germinant taurocholate relative to flora from untreated mice, indicating that the population of bile salt modifying bacteria differed between the two groups. Taken together, these data suggest that an in vivo-produced compound, likely bile salts, stimulates colony formation from C. difficile spores and that levels of this compound are influenced by the commensal gastrointestinal flora.
艰难梭菌是一种产芽孢的细菌，会引起抗生素相关性腹泻。为了产生毒素并导致疾病，艰难梭菌的芽孢必须在宿主体内发芽并生长为营养细胞。尽管已经鉴定出几种能够在体外使艰难梭菌芽孢发芽的化合物，但芽孢所响应的体内信号以前是未知的。对未经处理和用抗生素处理的小鼠的肠和盲肠提取物的检查表明，来自用抗生素处理的小鼠的提取物可以刺激芽孢从孢子形成更大程度的菌落。用考来烯胺（一种胆汁盐结合树脂）处理这些提取物会严重降低提取物刺激孢子形成菌落的能力。这一结果，以及发芽因子体积小、热稳定和水溶性的事实，支持了胆汁盐在体内刺激艰难梭菌芽孢发芽的观点。所有能够刺激高比例孢子形成菌落的提取物都比不能形成孢子的提取物具有更高的初级胆汁盐与次级胆汁盐的比例。此外，与未用抗生素处理的小鼠相比，用抗生素处理的小鼠的盲肠菌群对牛磺胆酸盐的修饰能力降低，表明两组之间的胆汁盐修饰细菌种群不同。综上所述，这些数据表明，一种体内产生的化合物，可能是胆汁盐，刺激艰难梭菌的孢子形成菌落，并且这种化合物的水平受共生胃肠道菌群的影响。
