Antibacterial activity of recombinant endolysin LysNOVA-I against growing/non-growing and planktonic/biofilm cultures of Staphylococcus aureus strains

Abstract

Objective: Bacteriophage-encoded endolysins have emerged as novel antibacterial strategies against antibiotic-resistant bacteria. We identified a bacteriophage-derived conserved sequence encoding an endolysin specific to Staphylococcus aureus. A recombinant endolysin (LysNOVA-I) was then produced, characterised and evaluated against methicillin-resistant Staphylococcus aureus (MRSA). Methods: The endolysin gene from phage ФvB_SauS-phiIPLA88 was cloned, expressed, and successfully purified using affinity chromatography. The activity of pure recombinant endolysin (rLysNOVA-I) was subsequently evaluated against growing and non-growing planktonic cells and biofilm cultures of international MRSA clones. A computational analysis was conducted to elucidate protein folding and obtain insight into the molecular mechanisms. Results: rLysNOVA-I exhibited bactericidal activity against both exponential and stationary growth phase S. aureus cells. rLysNOVA-I also prevented biofilm formation and degradation of established S. aureus biofilms. Notably, rLysNOVA-I was active against the MRSA clone ST398, which is of veterinary and clinical relevance. Conclusions: Our findings highlight the clinical potential of rLysNOVA-I as a therapeutic or complementary alternative to antibiotics against multidrug-resistant S. aureus infections in human and veterinary medicine.