Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection.
Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection.
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DOI：
10.1371/journal.ppat.1003356
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发表时间：
2013-05
期刊：
影响因子：
6.7
通讯作者：
Sorg JA
中科院分区：
文献类型：
--
作者：
Francis MB;Allen CA;Shrestha R;Sorg JA
艰难梭菌孢子必须在体内发芽，成为活跃生长的细菌，以产生疾病所必需的毒素。C.艰难梭菌孢子响应某些胆汁酸和甘氨酸在体外萌发。在其他孢子形成细菌中，嵌在孢子内膜内的蛋白质感测萌发剂的存在，并触发Ca++-吡啶二羧酸（Ca++-DPA）从孢子核心释放，随后水解孢子皮层（一种专门的肽聚糖）。基于对其他产孢细菌的萌发受体的同源性搜索，C。difficile可能使用独特的机制来识别萌发物。在这里，我们确定萌发特异性蛋白酶，CspC，作为C。艰难梭菌胆汁酸萌发受体的研究表明，胆汁酸介导的萌发对于建立艰难梭菌具有重要意义。艰难梭菌病的仓鼠感染模型。这些结果突出了胆汁酸在触发体内萌发中的重要性，并首次描述了一种C。艰难梭菌孢子萌发受体阻断胆汁酸与C.艰难梭菌孢子可能是新疗法的有吸引力的靶点。 艰难梭菌感染（CDI）在美国和其他国家稳步增加。C.艰难梭菌孢子是感染因子，经常污染环境表面。然而，C.艰难梭菌孢子必须在体内萌发以活跃生长的细菌。某些胆汁酸和甘氨酸是刺激C.艰难孢子萌发。而C.艰难梭菌孢子是已知的，这些化合物与什么相互作用仍然未知。在这里，我们确定了萌发特异性蛋白酶，CspC，作为胆汁酸萌发受体。In C.在艰难梭菌中，预测CspC不具有催化活性。然而，我们发现cspC的突变改变了萌发识别的特异性或废除了C。艰难孢子对胆汁酸的反应是发芽。此外，我们还发现C.艰难梭菌孢子对于在梭菌动物模型中建立感染是重要的。艰难病我们的研究结果表明，一个独特的机制，C。艰难梭菌孢子萌发通过孢子萌发剂直接刺激皮层水解。详细介绍了C.艰难梭菌CspC可能有助于鉴定萌发阻断化合物，其可能在阻碍C.艰难的殖民
Clostridium difficile spores must germinate in vivo to become actively growing bacteria in order to produce the toxins that are necessary for disease. C. difficile spores germinate in vitro in response to certain bile acids and glycine. In other sporulating bacteria, proteins embedded within the inner membrane of the spore sense the presence of germinants and trigger the release of Ca++-dipicolinic acid (Ca++-DPA) from the spore core and subsequent hydrolysis of the spore cortex, a specialized peptidoglycan. Based upon homology searches of known germinant receptors from other spore-forming bacteria, C. difficile likely uses unique mechanisms to recognize germinants. Here, we identify the germination-specific protease, CspC, as the C. difficile bile acid germinant receptor and show that bile acid-mediated germination is important for establishing C. difficile disease in the hamster model of infection. These results highlight the importance of bile acids in triggering in vivo germination and provide the first description of a C. difficile spore germinant receptor. Blocking the interaction of bile acids with the C. difficile spore may represent an attractive target for novel therapeutics. Clostridium difficile infections (CDI) are steadily increasing in the United States and other countries. C. difficile spores are the infectious agent and often contaminate environmental surfaces. However, to initiate infection, C. difficile spores must germinate in vivo to actively growing bacteria. Certain bile acids and glycine are the most effective compounds that stimulate C. difficile spore germination. While the signals that stimulate germination by C. difficile spores are known, with what these compounds interact remained unknown. Here, we identified the germination-specific protease, CspC, as the bile acid germinant receptor. In C. difficile, CspC is not predicted to have catalytic activity. However, we find that mutations in cspC alter the specificity of germinant recognition or abrogate the ability of C. difficile spore to germinate in response to bile acids. Further, we show that bile acid recognition by C. difficile spores is important for establishing infection in an animal model of C. difficile disease. Our results suggest a unique mechanism for C. difficile spore germination through direct stimulation of cortex hydrolysis by a spore germinant. A detailed understanding of germinant recognition by C. difficile CspC may aid in the identification of germination-blocking compounds, which may have importance in hindering C. difficile colonization.
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影响因子：
3.7
作者：
Giel JL;Sorg JA;Sonenshein AL;Zhu J
通讯作者：
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6.7
作者：
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158.5
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3.2
作者：
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通讯作者：
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影响因子：
--
作者：
Bouillaut, Laurent;McBride, Shonna M;Sorg, Joseph A
通讯作者：
Sorg, Joseph A