Designed antimicrobial peptides for recurrent vulvovaginal candidiasis treatment
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Microbiology
Abstract
Recurrent vulvovaginal candidiasis (RVVC) is a widespread chronic infection
that has a substantial negative impact on work and quality of life. The development
of antimicrobial resistance and biofilm formation are speculated to contribute
to Candida pathogenicity and treatment ineffectiveness. Designed antimicrobial peptides
(dAMPs) are chemically modified from endogenous antimicrobial peptides that
provide the first line of defense against pathogens. The goal here is to identify a
dAMP for the topical treatment of RVVC. The dAMP MICs were determined for 46
fluconazole-susceptible and fluconazole-resistant Candida spp. clinical isolates. The
possibility of inducing dAMP drug resistance and comparison of dAMP and fluconazole
activity against preformed Candida biofilm and biofilm formation were evaluated.
Assessment of mammalian cell viability was determined using bioluminescent
human keratinocytes. The dAMP effect on fungus was probed via scanning electron
microscopy, and topically applied dAMP activity was evaluated in a rodent vulvovaginal
candidiasis (VVC) infection model. dAMPs demonstrated broad-spectrum antimicrobial
activity against common causative clinical Candida isolates, reduced preformed
biofilm, and inhibited biofilm formation. An evaluated dAMP did not induce
resistance after repeated exposure of Candida tropicalis. The dAMPs were selective
for Candida cells with limited mammalian cytotoxicity with substantial activity in a
rodent VVC model. dAMPs are described as having potent antifungal and antibiofilm
activity, likely direct membrane action with selectivity for Candida cells, with limited
resistance development. Combined with activity in a rodent VVC model, the data
support clinical evaluation of dAMPs for topical treatment of VCC and recurrent VVC
infections.
Description
CITATION: Woodburn, K. W., et al. 2019. Designed antimicrobial peptides for recurrent vulvovaginal candidiasis treatment. Antimicrobial Agents and Chemotherapy, 63(11):e02690-18, doi:10.1128/AAC.02690-18.
The original publication is available at https://aac.asm.org
The original publication is available at https://aac.asm.org
Keywords
Antimicrobial peptides, Vulvovaginal candidiasis
Citation
Woodburn, K. W., et al. 2019. Designed antimicrobial peptides for recurrent vulvovaginal candidiasis treatment. Antimicrobial Agents and Chemotherapy, 63(11):e02690-18, doi:10.1128/AAC.02690-18