Vuong Cuong, Gerke Christiane, Somerville Greg A, Fischer Elizabeth R, Otto Michael
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
J Infect Dis. 2003 Sep 1;188(5):706-18. doi: 10.1086/377239. Epub 2003 Aug 11.
Staphylococcus epidermidis is the most frequent cause of nosocomial sepsis and catheter-related infections, in which biofilm formation is considered to be the main virulence mechanism. Quorum-sensing systems have been recognized as important regulators of virulence and biofilm formation in many bacteria. There is a single quorum-sensing system in S. epidermidis encoded by the agr operon. To investigate quorum-sensing control of biofilm formation, we constructed an agr deletion mutant, assayed for the different stages of biofilm formation, and determined agr-dependent regulation of biofilm factors. The agr mutant showed increased biofilm formation, primary attachment, and expression of the autolysin AtlE, but lacked delta-toxin production. However, the level of polysaccharide intercellular adhesin expression was equivalent to the isogenic wild-type strain. In contrast to AtlE, which is known to influence primary attachment, delta-toxin appeared to exert its effect on attachment to polystyrene during later stages of biofilm formation. Importantly, addition of cross-inhibiting pheromones mimicked an agr mutation and significantly enhanced biofilm formation, which suggests that care should be used when treating S. epidermidis infections with cross-inhibiting peptides. Our data demonstrate the importance of quorum sensing in the establishment of a biofilm in this critical human pathogen.
表皮葡萄球菌是医院败血症和导管相关感染最常见的病因，其中生物膜形成被认为是主要的致病机制。群体感应系统已被公认为许多细菌中致病性和生物膜形成的重要调节因子。表皮葡萄球菌中存在一个由agr操纵子编码的单一群体感应系统。为了研究群体感应对生物膜形成的控制，我们构建了一个agr缺失突变体，检测了生物膜形成的不同阶段，并确定了agr对生物膜因子的依赖性调节。agr突变体表现出生物膜形成增加、初始黏附增加以及自溶素AtlE的表达增加，但缺乏δ-毒素的产生。然而，多糖细胞间黏附素的表达水平与同基因野生型菌株相当。与已知影响初始黏附的AtlE不同，δ-毒素似乎在生物膜形成的后期阶段对聚苯乙烯的黏附发挥作用。重要的是，添加交叉抑制性信息素模拟了agr突变并显著增强了生物膜形成，这表明在用交叉抑制性肽治疗表皮葡萄球菌感染时应谨慎使用。我们的数据证明了群体感应在这种重要的人类病原体生物膜形成中的重要性。
