Department of Microbiology, University of Iowa, Iowa City, Iowa, USA.
Infect Immun. 2014 Jun;82(6):2345-55. doi: 10.1128/IAI.01483-13. Epub 2014 Mar 24.
Clostridium difficile is a clinically important pathogen and the most common cause of hospital-acquired infectious diarrhea. Expression of the C. difficile gene csfV, which encodes σ(V), an extracytoplasmic function σ factor, is induced by lysozyme, which damages the peptidoglycan of bacteria. Here we show that σ(V) is required for lysozyme resistance in C. difficile. Using microarray analysis, we identified the C. difficile genes whose expression is dependent upon σ(V) and is induced by lysozyme. Although the peptidoglycan of wild-type C. difficile is intrinsically highly deacetylated, we have found that exposure to lysozyme leads to additional peptidoglycan deacetylation. This lysozyme-induced deacetylation is dependent upon σ(V). Expression of pdaV, which encodes a putative peptidoglycan deacetylase, was able to increase lysozyme resistance of a csfV mutant. The csfV mutant strain is severely attenuated compared to wild-type C. difficile in a hamster model of C. difficile-associated disease. We conclude that the σ(V) signal transduction system, which senses the host innate immune defense enzyme lysozyme, is required for lysozyme resistance and is necessary during C. difficile infection.
艰难梭菌是一种临床上重要的病原体，也是医院获得性感染性腹泻的最常见原因。编码 σ(V)的艰难梭菌基因 csfV 的表达被溶菌酶诱导，溶菌酶会破坏细菌的肽聚糖。在这里，我们表明 σ(V)是艰难梭菌对溶菌酶产生抗性所必需的。通过微阵列分析，我们确定了依赖 σ(V)表达并被溶菌酶诱导的艰难梭菌基因。尽管野生型艰难梭菌的肽聚糖固有地高度去乙酰化，但我们发现暴露于溶菌酶会导致额外的肽聚糖去乙酰化。这种溶菌酶诱导的去乙酰化依赖于 σ(V)。表达编码潜在肽聚糖脱乙酰酶的 pdaV 能够增加 csfV 突变体对溶菌酶的抗性。与野生型艰难梭菌相比，csfV 突变株在艰难梭菌相关疾病的仓鼠模型中严重减毒。我们得出结论，感知宿主先天免疫防御酶溶菌酶的 σ(V)信号转导系统是对溶菌酶产生抗性所必需的，并且在艰难梭菌感染期间是必要的。
