Temasek Life Sciences Laboratory, Singapore, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
Commun Biol. 2024 Aug 6;7(1):947. doi: 10.1038/s42003-024-06617-4.
Clostridium septicum infections are highly predictive of certain malignancies in human patients. To initiate infections, C. septicum spores must first germinate and regain vegetative growth. Yet, what triggers the germination of C. septicum spores is still unknown. Here, we observe that C. septicum germinates in response to specific bile salts. Putative bile salt recognition genes are identified in C. septicum based on their similarity in sequence and organization to bile salt-responsive csp genes in Clostridioides difficile. Inactivating two of these csp orthologs (cspC-82 and cspC-1718) results in mutant spores that no longer germinate in the presence of their respective cognate bile salts. Additionally, inactivating the putative cspBA or sleC genes in C. septicum abrogates the germination response to all bile salt germinants, suggesting that both act at a convergent point downstream of cspC-82 and cspC-1718. Molecular dynamics simulations show that both CspC-82 and CspC-1718 bear a strong structural congruence with C. difficile's CspC. The existence of functional bile salt germination sensors in C. septicum may be relevant to the association between infection and malignancy.
梭状芽孢杆菌属（Clostridium） septicum 感染高度预测人类患者的某些恶性肿瘤。为了引发感染，梭状芽孢杆菌属 septicum 孢子必须首先发芽并恢复营养生长。然而，触发梭状芽孢杆菌属 septicum 孢子发芽的原因尚不清楚。在这里，我们观察到梭状芽孢杆菌属 septicum 对特定胆盐作出反应而发芽。基于序列和组织的相似性，我们在梭状芽孢杆菌属 septicum 中鉴定出了推测的胆盐识别基因，这些基因与艰难梭菌（Clostridioides difficile）中对胆盐有反应的 csp 基因相似。失活这两个 csp 直系同源物（cspC-82 和 cspC-1718）会导致突变体孢子在各自同源胆盐存在的情况下不再发芽。此外，在梭状芽孢杆菌属 septicum 中失活假定的 cspBA 或 sleC 基因会消除对所有胆盐发芽剂的发芽反应，表明这两者都在 cspC-82 和 cspC-1718 的下游共同作用。分子动力学模拟表明，CspC-82 和 CspC-1718 都与艰难梭菌的 CspC 具有很强的结构一致性。梭状芽孢杆菌属 septicum 中存在功能性胆盐发芽传感器可能与感染和恶性肿瘤之间的关联有关。
