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

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• A phage-derived endolysin (LysNOVA-I) was identified and recombinant production was conducted. • The recombinant endolysin (rLysNOVA-I) displayed activity against growing and non-growing planktonic S. aureus. • The endolysin effectively inhibited biofilm formation and degraded established biofilms. • Potent lytic activity was demonstrated against international MRSA clone ST398. • Clinical potential of rLysNOVA-I against MRSA in human and veterinary is discussed. Bacteriophage-encoded endolysins have emerged as novel antibacterial strategies against antibiotic-resistant bacteria. We identified a bacteriophage-derived conserved sequence encoding an endolysin specific against Staphylococcus aureus. Then a recombinant endolysin (LysNOVA-I) was produced, characterized and evaluated against methicillin-resistant Staphylococcus aureus (MRSA). Endolysin gene from phage ФvB_SauS-phiIPLA88was cloned, expressed, and successfully purified by 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 clones of MRSA. A computational analysis was conducted to elucidate the protein folding and obtain insight into the molecular mechanism. rLysNOVA-I exhibited bactericidal activity against both exponential growth and stationary growth phase S. aureus cells. rLysNOVA-I also prevents biofilm formation and degradation of established S. aureus biofilms. Noteworthy, the rLysNOVA-I was active against the MRSA clone ST398 of veterinary and clinical relevance. Our findings highlight the clinical potential of rLysNOVA-Ias a therapeutic or complementary alternative to the use of antibiotics to multidrug-resistant S. aureus infections in human and veterinary medicine.