An Ointment Consisting of the Phage Lysin LysGH15 and Apigenin for Decolonization of Methicillin-Resistant Staphylococcus aureus from Skin Wounds

Abstract

<i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a common and dangerous pathogen that causes various infectious diseases. Skin damage, such as burn wounds, are at high risk of <i>Staphylococcus aureus</i> colonization and infection, which increases morbidity and mortality. The phage lysin LysGH15 exhibits highly efficient lytic activity against methicillin-resistant <i>S. aureus</i> (MRSA) and methicillin-susceptible <i>S. aureus</i> (MSSA) strains. Apigenin (api) significantly decreases haemolysis of rabbit erythrocytes caused by <i>S. aureus</i> and shows anti-inflammatory function. LysGH15 and api were added to Aquaphor to form an LysGH15-api-Aquaphor (LAA) ointment. The LAA ointment simultaneously exhibited bactericidal activity against <i>S. aureus</i> and inhibited haemolysis. In an LAA-treated mouse model of an MRSA-infected skin wound, the mean bacterial colony count decreased to approximately 10² CFU/mg at 18 h after treatment (and the bacteria became undetectable at 96 h), whereas the mean count in untreated mice was approximately 10⁵ CFU/mg of tissue. The LAA ointment also reduced the levels of pro-inflammatory cytokines (TNF-&alpha;, IL-1&beta;, and IFN-&gamma;) and accelerated wound healing in the mouse model. These data demonstrate the potential efficacy of a combination of LysGH15 and api for use as a topical antimicrobial agent against <i>S. aureus</i>.