Evolution of virulence control by the staphylococcal agr quorum-sensing regulator

ABSTRACT: The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant

ORGANISM(S): Rickettsia rickettsii Staphylococcus epidermidis RP62A Coxiella burnetii RSA 493 Granulibacter bethesdensis Staphylococcus epidermidis ATCC 12228 Chlamydia muridarum Chlamydia trachomatis D/UW-3/CX Staphylococcus haemolyticus JCSC1435 Borreliella burgdorferi B31 Staphylococcus aureus Chlamydia pneumoniae AR39 Staphylococcus aureus subsp. aureus MW2 Coxiella burnetii Chlamydia caviae GPIC

PROVIDER: GSE10165 | GEO | 2009/01/05

SECONDARY ACCESSION(S): PRJNA108363

REPOSITORIES: GEO