Expression of Adhesive Pili and the Collagen-Binding Adhesin Ace Is Activated by ArgR Family Transcription Factors in Enterococcus faecalis

It was shown previously that the disruption of the gene encoding a predicted ArgR family transcription factor results in a severe defect in biofilm formation , as well as a significant attenuation of virulence of strain OG1RF in multiple experimental infection models. Using transcriptome sequencing (RNA-seq), we observed -dependent changes in the expression of more than 20 genes. AhrC-repressed genes included predicted determinants of arginine catabolism and several other metabolic genes and predicted transporters, while AhrC-activated genes included determinants involved in the production of surface protein adhesins. Most notably, the structural and regulatory genes of the locus encoding adhesive pili were positively regulated, as well as the gene, encoding a collagen-binding adhesin. Using transcription reporter fusions, we determined that and a second transcription factor gene, , both function to activate the expression of , which directly activates the transcription of the pilus structural genes. Our data suggest that in the wild-type , the low levels of EbpR limit the expression of pili and that biofilm biomass is also limited by the amount of pili expressed by the bacteria. The expression of is similarly enhanced by AhrC and ArgR2, but expression is not dependent on EbpR. Our results demonstrate the existence of novel regulatory cascades controlled by a pair of ArgR family transcription factors that might function as a heteromeric protein complex. Cell surface adhesins play critical roles in the formation of biofilms, host colonization, and the pathogenesis of opportunistic infections by Here, we present new results showing that the expression of two major enterococcal surface adhesins, pili, and the collagen-binding protein Ace is positively regulated at the transcription level by two family transcription factors, AhrC and ArgR2. In the case of pili, the direct target of regulation is the gene, previously shown to activate the transcription of the pilus structural genes, while the activation of transcription appears to be directly impacted by the two ArgR proteins. These transcription factors may represent new targets for blocking enterococcal infections.