Regulation of Biofilm Formation by σ B is a Common Mechanism in Staphylococcus Epidermidis and is not Mediated by Transcriptional Regulation of sarA

Abstract

Biofilm formation is a major pathogenetic factor of Staphylococcus epidermidis. In S. epidermidis the alternative sigma factor σ^B was identified to regulate biofilm formation in S. epidermidis 1457. In S. aureus σ^B dependent regulation plays a minor role, whereas sarA (Staphylococcus accessory regulator) is an essential regulator. Therefore, we investigated the impact of σ^B on sarA transcription and biofilm formation in three independent S. epidermidis isolates. Mutants with dysfunctional σ^B displayed a strongly reduced biofilm formation, whereas in mutants with constitutive σ^B activity bio film formation was increased. Transcriptional analysis revealed that IcaA transcription was down-regulated in all σ^B negative mutants while icaR transcription was up-regulated. However, transcriptional differences varied between individual strains, indicating that additional σ^B-dependent regulators are involved in biofilm expression. Interestingly, despite the presence of a σ^B promoter beside two σ^A promoters no differences, or only minor ones, were observed in sarA transcription, indicating that σ^B-dependent sarA transcript has no influence on the phenotypic changes. The data observed in independent clinical S. epidermidis isolates suggests that, in contrast to S. aureus, regulation of biofilm formation by σ^B is a general feature in S. epidermidis. Additionally, we were able to demonstrate that the sarA- dependent regulation is not involved in this regulatory pathway.