Abstract
One of the new strategies for the prevention of HIV acquisition is the use of microbicides such as topical microbicides including antimicrobial and antiviral peptides. Ideally, new drug candidates should kill pathogens without determent to the normal bacterial flora considered important in health; such as hydrogen peroxide producing Lactobacillus species. The antimicrobial peptides LL-37 and LSA-5 were studied to determine their spectrum of activity against bacterial pathogens and normal flora organisms. The effects of divalent cations at biologically relevant concentrations were determined. We show the synthetic lytic peptide LSA-5 and the naturally occurring peptides LL-37 inactivate Neisseria gonorrhoeae but are less active against many normal flora members such as Lactobacillus species. Biologically relevant concentrations of calcium and magnesium prevented killing of sensitive strains. LSA-5 is more potent than LL-37, both are inhibited from killing sensitive strains by calcium and magnesium. Strains of Lactobacillus iners were killed by both microbicides even in the presence of the divalent cations. Antimicrobial peptides, such as LSA-5, have good potential for use in prevention of sexually transmitted disease, if formulated to sequester calcium and magnesium present in biological fluids.
Highlights
Antimicrobial peptides, both host-derived and engineered, have great potential for the treatment and prevention of human diseases [1,2,3]
We show the synthetic lytic peptide LSA-5 and the naturally occurring peptides LL-37 inactivate Neisseria gonorrhoeae but are less active against many normal flora members such as Lactobacillus species
LSA-5 is more potent than LL-37, both are inhibited from killing sensitive strains by calcium and magnesium
Summary
Antimicrobial peptides, both host-derived and engineered, have great potential for the treatment and prevention of human diseases [1,2,3]. The rapid development of antibiotic resistance among many of the important pathogens extends the potential application of peptides to include topical and systemic uses. Internal uses such as intravenous or as a topical vaginal microbicides introduce the possibility of interference or inactivation by endogenous factors present in plasma or vaginal fluid. Microbicides are evaluated by their killing efficacy, which describes the drug concentration required to reduce viability by 99.99% (a four log reduction) in a given time. This differs from conventional antibiotics where inhibition of growth is used to determine activity [4]
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