Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
J Clin Invest. 2011 Jan;121(1):238-48. doi: 10.1172/JCI42520. Epub 2010 Dec 6.
Biofilms are surface-attached agglomerations of microorganisms embedded in an extracellular matrix. Biofilm-associated infections are difficult to eradicate and represent a significant reservoir for disseminating and recurring serious infections. Infections involving biofilms frequently develop on indwelling medical devices in hospitalized patients, and Staphylococcus epidermidis is the leading cause of infection in this setting. However, the molecular determinants of biofilm dissemination are unknown. Here we have demonstrated that specific secreted, surfactant-like S. epidermidis peptides--the β subclass of phenol-soluble modulins (PSMs)--promote S. epidermidis biofilm structuring and detachment in vitro and dissemination from colonized catheters in a mouse model of device-related infection. Our study establishes in vivo significance of biofilm detachment mechanisms for the systemic spread of biofilm-associated infection and identifies the effectors of biofilm maturation and detachment in a premier biofilm-forming pathogen. Furthermore, by demonstrating that antibodies against PSMβ peptides inhibited bacterial spread from indwelling medical devices, we have provided proof of principle that interfering with biofilm detachment mechanisms may prevent dissemination of biofilm-associated infection.
生物膜是微生物附着在表面并嵌入细胞外基质中的聚集物。生物膜相关感染难以根除,是传播和反复发生严重感染的重要来源。在住院患者中,与生物膜相关的感染常发生在留置的医疗设备上,表皮葡萄球菌是该环境中感染的主要原因。然而,生物膜传播的分子决定因素尚不清楚。在这里,我们已经证明了特定分泌的、表面活性剂样的表皮葡萄球菌肽——酚可溶性调节素(PSM)的β亚类——在体外促进表皮葡萄球菌生物膜的结构和脱落,并在与器械相关感染的小鼠模型中从定植的导管中传播。我们的研究确立了生物膜脱落机制对生物膜相关感染系统性传播的体内重要性,并确定了在主要生物膜形成病原体中生物膜成熟和脱落的效应物。此外,通过证明针对 PSMβ肽的抗体抑制了留置医疗器械中细菌的扩散,我们提供了一个原理证明,即干扰生物膜脱落机制可能防止生物膜相关感染的传播。