Microbicidal Effects of α- and θ-Defensins Against Antibiotic-Resistant Staphylococcus aureus and Pseudomonas aeruginosa

Authors

Kenneth P. Tai, University of Southern CaliforniaFollow
Karishma Kamdar, University of Southern California
Jason Yamaki, Chapman UniversityFollow
Valerie V. Le, University of Southern California
Dat Tran, University of Southern California
Patti Tran, University of Southern California
Michael E. Selsted, University of Southern California
Andre J. Ouelette, University of Southern California
Annie Wong-Beringer, University of Southern California

Document Type

Article

Publication Date

12-17-2013

Abstract

Antibiotic-resistant bacterial pathogens threaten public health. Because many antibiotics target specific bacterial enzymes or reactions, corresponding genes may mutate under selection and lead to antibiotic resistance. Accordingly, antimicrobials that selectively target overall microbial cell integrity may offer alternative approaches to therapeutic design. Naturally occurring mammalian α- and θ-defensins are potent, non-toxic microbicides that may be useful for treating infections by antibiotic-resistant pathogens because certain defensin peptides disrupt bacterial, but not mammalian, cell membranes. To test this concept, clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), including vancomycin heteroresistant strains, and ciprofloxacin-resistant Pseudomonas aeruginosa (Cip^R-PA) were tested for sensitivity to α-defensins Crp-4, RMAD-4 and HNPs 1-3, and to RTD-1, macaque θ-defensin-1. In vitro, 3 μM Crp-4, RMAD-4 and RTD-1 reduced MRSA cell survival by 99%, regardless of vancomycin susceptibility. For PA clinical isolates that differ in fluoroquinolone resistance and virulence phenotype, peptide efficacy was independent of strain ciprofloxacin resistance, site of isolation or virulence factor expression. Thus, Crp-4, RMAD-4 and RTD-1 are effective in vitro antimicrobials against clinical isolates of MRSA and Cip^R-PA, perhaps providing templates for development of α- and θ-defensin-based microbicides against antibiotic resistant or virulent infectious agents.

Comments

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Innate Immunity, volume 21, issue 1, in 2015 following peer review. The definitive publisher-authenticated version is available online at DOI: 10.1177/1753425913514784.

Recommended Citation

Tai KP, Kamdar K, Yamaki J, et al. Microbicidal effects of α- and θ-defensins against antibiotic-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Innate Immun. 2015;21(1):17-29. doi:10.1177/1753425913514784.

Copyright

The authors