Endolysin LysSte134_1 Reduces Staphylococcus Bacterial Load in Infected Wounds In Vivo

Abstract

Staphylococcus aureus is an ESKAPE pathogen, defined by its ability to evade antibacterial treatment, and together with S. epidermidis is a leading Gram-positive cause of wound infection. The emergence of methicillin- and vancomycin-resistant strains further limits conventional antibiotic treatment. The staphylococcal endolysin LysSte134_1 was produced recombinantly, its proper folding confirmed by zymography, and its lytic activity demonstrated against planktonic cultures of both S. aureus and S. epidermidis. The combination of LysSte134_1 with 10% 1,3-propanediol and Zn2+ increased CFU reduction in both species relative to LysSte134_1 with Zn2+ alone. In a murine wound model, topical application of LysSte134_1 significantly reduced the bacterial burden in wound tissue, achieving a 2–3-log reduction in MRSA and below the detection limit for S. epidermidis. Treatment was accompanied by normalization of peripheral leukocyte counts and a shift in the serum cytokine profile from a sustained pro-inflammatory state with elevated IL-6, IL-17 and IL-10 toward levels comparable to non-infected controls. These results suggest the potential utility of LysSte134_1 as a component of topical antibacterial formulations and support further investigation in models of staphylococcal wound infection.