Designed antimicrobial peptides for recurrent vulvovaginal candidiasis treatment

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dc.contributor.authorWoodburn, Kathryn W.en_ZA
dc.contributor.authorClemens, L. Edwarden_ZA
dc.contributor.authorJaynes, Jesseen_ZA
dc.contributor.authorJoubert, Lydia-Marieen_ZA
dc.contributor.authorBotha, Alfreden_ZA
dc.contributor.authorNazik, Hasanen_ZA
dc.contributor.authorStevense, David A.en_ZA
dc.date.accessioned2021-07-16T10:55:50Z
dc.date.available2021-07-16T10:55:50Z
dc.date.issued2019
dc.descriptionCITATION: 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.
dc.descriptionThe original publication is available at https://aac.asm.org
dc.description.abstractRecurrent 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.en_ZA
dc.description.urihttps://journals.asm.org/doi/10.1128/AAC.02690-18
dc.description.versionPublisher's version
dc.format.extent11 page : illustrationsen_ZA
dc.identifier.citationWoodburn, 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
dc.identifier.issn1098-6596 (online)
dc.identifier.issn0066-4804 (print)
dc.identifier.otherdoi:10.1128/AAC.02690-18
dc.identifier.urihttp://hdl.handle.net/10019.1/110736
dc.language.isoen_ZAen_ZA
dc.publisherAmerican Society for Microbiology
dc.rights.holderAuthors retain copyright
dc.subjectAntimicrobial peptidesen_ZA
dc.subjectVulvovaginal candidiasisen_ZA
dc.titleDesigned antimicrobial peptides for recurrent vulvovaginal candidiasis treatmenten_ZA
dc.typeArticleen_ZA
dcterms.abstractFungicidal activityen_ZA
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