Staphylococcus aureusSusceptibility to Innate Antimicrobial Peptides, β-Defensins and CAP18, Expressed by Human Keratinocytes

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Abstract
The antimicrobial peptides human β-defensin-1 (hBD1), hBD2, hBD3, and CAP18 expressed by keratinocytes have been implicated in mediation of the innate defense against bacterial infection. To gain insight intoStaphylococcus aureusinfection, the susceptibility ofS. aureus, including methicillin-resistantS. aureus(MRSA), to these antimicrobial peptides was examined. Based on quantitative PCR, expression of hBD2 mRNA by human keratinocytes was significantly induced by contact withS. aureus, and expression of hBD3 and CAP18 mRNA was slightly induced, while hBD1 mRNA was constitutively expressed irrespective of the presence ofS. aureus. Ten clinicalS. aureusisolates, including five MRSA isolates, induced various levels of expression of hBD2, hBD3, and CAP18 mRNA by human kertinocytes. The activities of hBD3 and CAP18 againstS. aureuswere found to be greater than those of hBD1 and hBD2. A total of 44S. aureusclinical isolates, including 22 MRSA strains, were tested for susceptibility to hBD3 and CAP18. Twelve (55%) and 13 (59%) of the MRSA strains exhibited more than 20% survival in the presence of hBD3 (1 μg/ml) and CAP18 (0.5 μg/ml), respectively. However, only three (13%) and two (9%) of the methicillin-sensitiveS. aureusisolates exhibited more than 20% survival with hBD3 and CAP18, respectively, suggesting that MRSA is more resistant to these peptides. A synergistic antimicrobial effect between suboptimal doses of methicillin and either hBD3 or CAP18 was observed with 10 MRSA strains. Furthermore, of several genes associated with methicillin resistance, inactivation of thefmtCgene in MRSA strain COL increased susceptibility to the antimicrobial effect mediated by hBD3 or CAP18.

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