Global analysis of transcriptional regulators in Staphylococcus aureus

Staphylococcus aureus is a widely distributed human pathogen capable of infecting almost every ecological niche of the host. As a result, it is responsible for causing many different diseases. S. aureus has a vast array of virulence determinants whose expression is modulated by an intricate regulatory network, where transcriptional factors (TFs) are the primary elements. In this work, using diverse sequence analysis, we evaluated the repertoire of TFs and sigma factors in the community-associated methicillin resistant S. aureus (CA-MRSA) strain USA300-FPR3757.

A total of 135 TFs and sigma factors were identified and classified into 36 regulatory families. From these around 43% have been experimentally characterized to date, which demonstrates the significant work still at hand to unravel the regulatory network in place for this important pathogen. A comparison of the TF repertoire of S. aureus against 1209 sequenced bacterial genomes was carried out allowing us to identify a core set of orthologous TFs for the Staphylococacceae, and also allowing us to assign potential functions to previously uncharacterized TFs. Finally, the USA300 TFs were compared to those in eleven other S. aureus strains including: Newman, COL, JH1, JH9, MW2, Mu3, Mu50, N315, RF122, MRSA252 and MSSA476. We identify conserved TFs among these strains and suggest possible regulatory interactions.

The analysis presented herein highlights the complexity of regulatory networks in S. aureus strains, identifies key conserved TFs among the Staphylococacceae, and offers unique insights into several as yet uncharacterized TFs.