Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide

The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a serious health concern worldwide that requires new therapeutic approaches that extend beyond the development and use of new antibiotics. In this study, a conformationally biased, response-selective agonist of human C5a, known as EP67, was used to induce host innate immunity as a therapeutic method of reducing CA-MRSA infections. Using a murine model of dermonecrosis we show that EP67 treatment effectively limits CA-MRSA infection by promoting cytokine synthesis and neutrophil influx. In contrast, EP67 was ineffective in reducing lesion formation in C5a receptor (CD88−/−) knockout mice, indicating that EP67 activates host innate immunity by engagement of CD88 bearing cells. These results suggest that EP67 may serve as a novel immunotherapeutic for prevention and treatment of CA-MRSA dermal infection.

► We study a conformationally biased, response-selective agonist of human C5a, EP67, as a therapeutic method of reducing CA-MRSA infections.
► We show that EP67 treatment effectively limits CA-MRSA infection by promoting cytokine synthesis and neutrophil influx.
► These results suggest that EP67 may serve as a novel immunotherapy for CA-MRSA dermal infection.