Ygs Is a Novel Gene That Influences Biofilm Formation and the General Stress Response of Staphylococcus epidermidis

Abstract

Infections caused by the nosocomial pathogen Staphylococcus epidermidis frequently develop on implanted medical devices and involve biofilm formation. Biofilms are surface-attached microbial communities that show increased resistance to drug treatment and mechanisms of innate host defense. In this study, a mutant library of the clinical isolate S. epidermidis 1457 was constructed using mariner-based transposon mutagenesis. About a thousand mutants were screened, and 12 mutants were identified as significantly defective in biofilm formation. We focused on a mutant in which the transposon had inserted in a gene with unknown function, SERP0541, which is annotated as a gene encoding a GSP13-like general stress response protein. The gene was named ygs (encoding an unknown general stress protein). Various stresses, including heat, pH, high osmolarity, and ethanol affected the survival of the ygs mutant to a significantly higher degree than the wild-type strain and led to increased expression of ygs. Furthermore, synthesis of polysaccharide intercellular adhesin (PIA) and transcription of the PIA biosynthetic operon were significantly decreased in the ygs mutant. These results are in accordance with the putative involvement of ygs in stress-response gene regulation and indicate that ygs influences biofilm development by controlling PIA-dependent biofilm accumulation. Moreover, ygs had a significant impact on the formation of biofilms and metastatic disease in two catheter-related rat infection models. Our study shows that the ygs gene controls S. epidermidis biofilm accumulation and stress resistance, representing a key regulator of both structural and physiological biofilm characteristics with a significant impact on biofilm-associated infection.