Differential Expression of the apsXRS System by Antimicrobial Peptide LL-37 in Commensal and Clinical Staphylococcus epidermidis Isolates.

ABSTRACT

The three-component apsXRS system senses and responds to cationic antimicrobial peptides (CAMPs), which induces the expression of the dlt operon and the genes mprF and vrafG, modifying the surface net charge in Staphylococcus epidermidis, resulting in the repulsion of CAMPs. The apsXRS system has been only studied in the S. epidermidis 1457 strain, and there are no studies of prevalence and level of expression of apsXRS in commensal and clinical isolates. From 60 isolates, those selected from commensal healthy skin (n = 20), commensal healthy conjunctive (n = 10), and clinical ocular infection (n = 30) presented the apsX, apsR, and apsS genes in their genomes. Constitutive expression of apsX, apsR, and apsS genes was determined by RT-qPCR in all isolates. It was found that expression of apsX, apsR, and apsS was 3.3-5.9-fold higher in commensal isolates stimulated with LL-37 (15 µg/mL) than in clinical isolates. Similarly, expression of the dlt operon and the genes mprF, and vraFG was 8-10-fold higher in commensal isolates than in clinical. However, LL-37 did not increase the addition of lysine in the phospholipids of the cytoplasmic membrane in any of the isolates. Mutations in the apsS loop region, apsR, and their promoter sequence were not found. These results demonstrated that apsXRS system is essential in all isolates for its constitutive expression; however, LL-37 caused an increase of apsXRS expression in commensal isolates, suggesting that S. epidermidis isolates do not respond in the same way to the presence of LL-37.