Identification of a Novel Two-Peptide Lantibiotic from Vagococcus fluvialis

Infections caused by multiresistant pathogens have become a major problem in both human and veterinary medicine. Due to the declining efficacy of many antibiotics, new antimicrobials are needed. Promising alternatives or additions to antibiotics are bacteriocins, antimicrobial peptides of bacterial origin with activity against many pathogens, including antibiotic-resistant strains. From a sample of fermented maize, we isolated a Vagococcus fluvialis strain producing a bacteriocin with antimicrobial activity against multiresistant Enterococcus faecium. Whole-genome sequencing revealed the genes for a novel two-peptide lantibiotic. The production of the lantibiotic by the isolate was confirmed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, which revealed distinct peaks at 4,009.4 m/z and 3,181.7 m/z in separate fractions from reversed-phase chromatography. The combination of the two peptides resulted in a 1,200-fold increase in potency, confirming the two-peptide nature of the bacteriocin, named vagococcin T. The bacteriocin was demonstrated to kill sensitive cells by the formation of pores in the cell membrane, and its inhibition spectrum covers most Gram-positive bacteria, including multiresistant pathogens. To our knowledge, this is the first bacteriocin characterized from Vagococcus. IMPORTANCE Enterococci are common commensals in the intestines of humans and animals, but in recent years, they have been identified as one of the major causes of hospital-acquired infections due to their ability to quickly acquire virulence and antibiotic resistance determinants. Many hospital isolates are multiresistant, thereby making current therapeutic options critically limited. Novel antimicrobials or alternative therapeutic approaches are needed to overcome this global problem. Bacteriocins, natural ribosomally synthesized peptides produced by bacteria to eliminate other bacterial species living in a competitive environment, provide such an alternative. In this work, we purified and characterized a novel two-peptide lantibiotic produced by Vagococcus fluvialis LMGT 4216 isolated from fermented maize. The novel lantibiotic showed a broad spectrum of inhibition of Gram-positive strains, including vancomycin-resistant Enterococcus faecium, demonstrating its therapeutic potential.