Interaction of contraceptive antimicrobial peptide nisin with target cell membranes: implications for use as vaginal microbicide
Gupta, S.M.; Aranha, C.C.; Bellare, J.R.; Reddy, K.V.R.
Contraception 80(3): 299-307
2009
ISSN/ISBN: 1879-0518 PMID: 19698825 DOI: 10.1016/j.contraception.2009.03.012Document Number: 207207
Nisin, a naturally occurring antimicrobial peptide (AMP), is currently the focus of clinical trials as an intravaginal microbicide. Therefore its mechanism of interaction with various cell membranes was studied. Flow cytometry was used for quantitative estimation of membrane damage by nisin which was further determined by scanning electron microscopy (SEM). Affinity of nisin for different unilamellar liposome vesicles was determined spectroflurometrically and confirmed using laser scanning confocal microscopy (LSCM). Propidium iodide (PI) staining by flow cytometry exhibited selective membrane permeabilizing effect of nisin on sperm and bacterial membranes which correlated with ultrastructural changes. In vitro interaction of nisin with liposome model vesicles revealed significant leakage of calcein from liposomes composed of phosphatidylcholine/phosphatidylglycerol (POPC/POPG) (e.g., bacteria) and phosphatidylcholine/phosphatidylserine (POPC/POPS) (e.g., spermatozoa) as compared to phosphatidylcholine/phosphatidylethanolamine (POPC/POPE) vesicles (e.g., red blood corpuscles). LSCM results were in complete agreement with cell membrane affinity studies. This unique property of nisin can be exploited in the development of a safe and effective vaginal microbicide for the prevention of sexually transmitted infections/acquired immunodeficiency syndrome (STIs/AIDS) and unplanned pregnancies.
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