Mode of action and safety of lactosporin.pdfVIP

Mode of action and safety of lactosporin, a novel antimicrobial protein produced by Bacillus coagulans ATCC 7050 Shadi Riazi1, Sara E. Dover2, and Michael L. Chikindas1,* 1School of Environmental and Biological Sciences, Rutgers State University, New Brunswick, New Jersey 08901, USA 2The Royal Institute of Technology, Stockholm, Sweden Abstract Aims—To determine the mechanism of action of antimicrobial protein, lactosporin, against Gardnerella vaginalis and to evaluate its safety in-vitro. Methods and Results—Bacillus coagulans ATCC 7050 was grown at 37 °C for 18 hours. The cell free supernatant was concentrated 10-fold and screened for antimicrobial activity against indicator strain Micrococcus luteus. The mode of action of lactosporin was determined by measuring the potassium release and monitoring the changes in transmembrane potential (Δψ) and transmembrane pH (ΔpH) of the sensitive cells. Lactosporin caused efflux of potassium ions from M. luteus cells and dissipation of ΔpH in G. vaginalis while it had no effect on the Δψ. The safety of lactosporin was evaluated by using EpiVaginal? ectocervical (VEC-100) tissue model. Over 80% of the cells in the vaginal tissue remained viable after exposure to lactosporin for 24 hours. Conclusions—Lactosporin potentially exerts its antimicrobial activity by selective dissipation of ΔpH and/or by causing leakage of ions from the sensitive cells. Safety studies suggest that lactosporin is a non-cytotoxix antimicrobial for vaginal application. Significance and Impact of the Study—This study revealed that lactosporin is an effective and safe antimicrobial preparation with potential application for control of bacterial vaginosis. Introduction Bacteriocins are ribosomally-synthesized antimicrobial compounds of proteinaceous nature produced by virtually all microorganisms that act against closely related species (Klaenhammer 1993). Bacteriocins produced by lactic acid bacteria (LAB) have received great attention in the past decade