Wang Li, Li Min, Dong Dandan, Bach Thanh-Huy L, Sturdevant Daniel E, Vuong Cuong, Otto Michael, Gao Qian
Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
J Infect Dis. 2008 May 1;197(9):1254-62. doi: 10.1086/586714.
Biofilm-associated infection due to Staphylococcus epidermidis, the leading nosocomial pathogen, is a major problem for the public health system, but the regulation of this important phenotype is not completely understood. Using a highly discriminatory screening procedure for genes that influence biofilm formation, we identified the transcriptional regulator SarZ as a novel important determinant of biofilm formation and biofilm-associated infection, on the basis of the significant impact of sarZ on the transcription of the biosynthetic operon for biofilm exopolysaccharide. In addition, sarZ influenced the expression of a series of virulence genes, including genes that influence the expression of lipases and proteases, resistance to an important human antimicrobial peptide, and hemolysis. Our study indicates that the SarZ regulator has a key role in maintaining the typical S. epidermidis phenotype, which is characterized by pronounced biofilm formation and immune evasion, a likely reason for the success of S. epidermidis as a colonizing organism and pathogen in chronic, biofilm-associated infection.
由表皮葡萄球菌引起的生物膜相关感染是公共卫生系统面临的一个重大问题,表皮葡萄球菌是主要的医院病原体,但对这一重要表型的调控尚未完全了解。我们采用一种高度有区分性的筛选程序来筛选影响生物膜形成的基因,基于sarZ对生物膜胞外多糖生物合成操纵子转录的显著影响,我们确定转录调节因子SarZ是生物膜形成和生物膜相关感染的一个新的重要决定因素。此外,sarZ影响一系列毒力基因的表达,包括影响脂肪酶和蛋白酶表达的基因、对一种重要的人类抗菌肽的抗性以及溶血相关基因。我们的研究表明,SarZ调节因子在维持典型的表皮葡萄球菌表型中起关键作用,该表型的特征是显著的生物膜形成和免疫逃避,这可能是表皮葡萄球菌作为慢性生物膜相关感染中的定植菌和病原体取得成功的一个原因。