The novel bacteriocin romsacin from Staphylococcus haemolyticus inhibits Gram-positive WHO priority pathogens

Abstract

Staphylococcus haemolyticus is an increasingly relevant nosocomial pathogen. The combination of multi-drug resistance and ability to form biofilms makes S. haemolyticus infections difficult to treat. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria to inhibit growth of often closely related bacteria. Due to differences in the modes of action between bacteriocins and antibiotics, bacteriocins are normally equally potent against antibiotic-resistant and antibiotic-sensitive strains. To find bacteriocins able to inhibit S. haemolyticus and related species, clinical and commensal S. haemolyticus isolates (n = 174) were assayed for bacteriocin production. One commensal isolate produced an antimicrobial substance inhibiting S. haemolyticus and Staphylococcus aureus. The substance had physicochemical properties that are characteristic of bacteriocins. Purification, whole-genome sequencing, and mass spectrometry identified the antimicrobial as a novel two-peptide lantibiotic, hereafter named romsacin. The bacteriocin was active against a broad range of Gram-positive bacteria, such as the World Health Organization priority pathogens S. aureus [methicillin-resistant S. aureus (MRSA)] and Enterococcus faecium [vancomycin-resistant E. faecium (VRE)]. Importantly, the bacteriocin also eradicated S. haemolyticus, Staphylococcus epidermidis, MRSA, and VRE biofilms.