Staphylococcus aureus competence genes: mapping of the SigH, ComK1 and ComK2 regulons by transcriptome sequencing

Staphylococcus aureus is a major human pathogen. Hospital infections caused by methicillin-resistant strains (MRSA), which have acquired resistance to a broad spectrum of antibiotics through horizontal gene transfer (HGT), are of particular concern. In S. aureus, virulence and antibiotic resistance genes are often encoded on mobile genetic elements that are disseminated by HGT. Conjugation and phage transduction have long been known to mediate HGT in this species, but it is unclear whether natural genetic transformation contributes significantly to the process. Recently, it was reported that expression of the alternative sigma factor SigH induces the competent state in S. aureus. The transformation efficiency obtained, however, was extremely low, indicating that the optimal conditions for competence development had not been found. We therefore used transcriptome sequencing to determine whether the full set of genes known to be required for competence in other naturally transformable bacteria is part of the SigH regulon. Our results show that several essential competence genes are not controlled by SigH. This presumably explains the low transformation efficiency previously reported, and demonstrates that additional regulating mechanisms must be involved. We found that one such mechanism involves ComK1, a transcriptional activator that acts synergistically with SigH.