Department of Biology, Texas A&M University, College Station, TX, 77843, USA.
NPJ Biofilms Microbiomes. 2022 Nov 30;8(1):94. doi: 10.1038/s41522-022-00358-0.
The Clostridioides difficile pathogen is responsible for nosocomial infections. Germination is an essential step for the establishment of C. difficile infection (CDI) because toxins that are secreted by vegetative cells are responsible for the symptoms of CDI. Germination can be stimulated by the combinatorial actions of certain amino acids and either conjugated or deconjugated cholic acid-derived bile salts. During synthesis in the liver, cholic acid- and chenodeoxycholic acid-class bile salts are conjugated with either taurine or glycine at the C24 carboxyl. During GI transit, these conjugated bile salts are deconjugated by microbes that express bile salt hydrolases (BSHs). Here, we surprisingly find that several C. difficile strains have BSH activity. We observed this activity in both C. difficile vegetative cells and in spores and that the observed BSH activity was specific to taurine-derived bile salts. Additionally, we find that this BSH activity can produce cholate for metabolic conversion to deoxycholate by C. scindens. The C. scindens-produced deoxycholate signals to C. difficile to initiate biofilm formation. Our results show that C. difficile BSH activity has the potential to influence the interactions between microbes, and this could extend to the GI setting.
艰难梭菌病原体是导致医院感染的原因。发芽是艰难梭菌感染（CDI）建立的一个必要步骤，因为由营养细胞分泌的毒素是导致 CDI 症状的原因。发芽可以通过某些氨基酸的组合作用和结合或非结合的胆酸衍生的胆汁盐来刺激。在肝脏合成过程中，胆酸和鹅脱氧胆酸类胆汁盐在 C24 羧基处与牛磺酸或甘氨酸结合。在 GI 转运过程中，表达胆汁盐水解酶（BSH）的微生物会使这些结合的胆汁盐脱结合。在这里，我们惊讶地发现几种艰难梭菌菌株具有 BSH 活性。我们在艰难梭菌营养细胞和孢子中观察到这种活性，并且观察到的 BSH 活性特异性针对牛磺酸衍生的胆汁盐。此外，我们发现这种 BSH 活性可以产生胆酸盐，供 C. scindens 进行代谢转化为脱氧胆酸盐。C. scindens 产生的脱氧胆酸盐向艰难梭菌发出信号，启动生物膜形成。我们的研究结果表明，艰难梭菌 BSH 活性有可能影响微生物之间的相互作用，并且这种相互作用可能会扩展到 GI 环境中。
