SarZ is a key regulator of biofilm formation and virulence in Staphylococcus epidermidis

Biofilm-associated infection by the leading nosocomial pathogen Staphylococcus epidermidis is a major problem for the public health system. Here we used an especially discriminatory, two-step screen to discover key biofilm factors. We identified the transcriptional regulator and SarA paralog SarZ as a novel important determinant of biofilm formation and biofilm-associated infection by S. epidermidis. Notably, a sarZ mutant strain exhibited significantly reduced survival in two different models of biofilm-associated infection. Further, in addition to its significant influence on the transcription of the biosynthetic operon for S. epidermidis biofilm exopolysaccharide, sarZ impacted the expression of a series of virulence factors, including lipases and proteases. As a likely consequence of the regulated proteolytic activity, we observed increased resistance to an important human antimicrobial peptide, indicating a role for sarZ in the regulation of immune evasion. Interestingly, sarZ deficiency led to a hemolytic phenotype, a feature not commonly observed in S. epidermidis. Thus, our study indicates a key role for the SarZ regulator in maintaining the typical S. epidermidis phenotype, which is characterized by pronounced biofilm formation, immune evasion, and suppressed acute virulence, a likely reason for the success of S. epidermidis as a colonizer and pathogen in chronic, biofilm-associated infection. Keywords: Wild type control vs mutant Wild type untreated in triplicate is compared to SarZ mutant in triplicate