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Role of the luxS Quorum-Sensing System in Biofilm Formation and Virulence of Staphylococcus epidermidis

Lin Xu,^1,2 Hualin Li,^1,2 Cuong Vuong,^3, Viveka Vadyvaloo,³ Jianping Wang,^1,2 Yufeng Yao,³ Michael Otto,³ and Qian Gao^1,2*

Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China,¹ Institute of Medical Microbiology, Fudan University, Shanghai 200032, People's Republic of China,² Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, the National Institutes of Health, Hamilton, Montana 59840³

Received 12 June 2005/ Returned for modification 18 July 2005/ Accepted 5 October 2005

Nosocomial infections caused by Staphylococcus epidermidis are characterized by biofilm formation on implanted medical devices. Quorum-sensing regulation plays a major role in the biofilm development of many bacterial pathogens. Here, we describe luxS, a quorum-sensing system in staphylococci that has a significant impact on biofilm development and virulence. We constructed an isogenic luxS mutant strain of a biofilm-forming clinical isolate of S. epidermidis and demonstrated that luxS signaling is functional in S. epidermidis. The mutant strain showed increased biofilm formation in vitro and enhanced virulence in a rat model of biofilm-associated infection. Genetic complementation and addition of autoinducer 2-containing culture filtrate restored the wild-type phenotype, demonstrating that luxS repressed biofilm formation through a cell-cell signaling mechanism based on autoinducer 2 secretion. Enhanced production of the biofilm exopolysaccharide polysaccharide intercellular adhesin in the mutant strain is presumably the major cause of the observed phenotype. The agr quorum-sensing system has previously been shown to impact biofilm development and biofilm-associated infection in a way similar to that of luxS, although by regulation of different factors. Our study indicates a general scheme of quorum-sensing regulation of biofilm development in staphylococci, which contrasts with that observed in many other bacterial pathogens.

Editor: F. C. Fang

Present address: Department of Anesthesiology, University of Massachusetts, Worster, MA 01655.

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