Anti-staphylococcal activity of a cyclic lipopeptide, C₁₅-bacillomycin D, produced by Bacillus velezensis NST6

Aim: The aim of this study was to assess antibacterial activity of a novel Bacillus velezensis strain NST6, and further identify its active compound against pathogenic Staphylococcus strains for clinical therapeutic applications. Methods and Results: In this study, a novel B. velezensis strain NST6 harbouring strong antimicrobial activity against human pathogenic bacteria was isolated from a soil sample. The solvent extract of the strain exhibited strong antibacterial activity against Gram-positive and Gram-negative bacteria in disc diffusion assay and measurement of minimal inhibitory concentration and bactericidal concentration, of which it showed notable efficacy to Staphylococcus species including Staphylococcus epidermidis, Staphylococcus aureus and methicillin-resistant S. aureus. Strong antibacterial effect against pathogenic S. aureus and low toxicity of the bacterial extract were further validated in Caenorhabditis elegans model. Moreover, by antibacterial activity-guided fractionation using RP-HPLC and LC-MS, we defined C₁₅-bacillomycin D as the anti-staphylococcal compound produced by the strain. Conclusion: The primary anti-staphylococcal compound from B. velezensis NST6 was identified as a cyclic lipopeptide, C₁₅-bacillomycin D, which proved its potential to treat Staphylococcus strains in vitro and in vivo experiments with insignificant level of toxicity. Significance and Impact of the Study: We provide an alternative treatment option to Staphylococcus infections by investigating the specific anti-staphylococcal activity of C₁₅-bacillomycin D produced by a B. velezensis strain.