title: Antifungal peptides: a potential new class of antifungals for treating vulvovaginal candidiasis caused by fluconazole-resistant Candida albicans.
abstract: Vulvovaginal candidiasis/candidosis is a common fungal infection afflicting approximately 75% of women globally caused primarily by the yeast Candida albicans. Fluconazole is widely regarded as the antifungal drug of choice since its introduction in 1990 due to its high oral bioavailability, convenient dosing regimen and favourable safety profile. However, its widespread use has led to the emergence of fluconazole-resistant C. albicans, posing a universal clinical concern. Coupled to the dearth of new antifungal drugs entering the market, it is imperative to introduce new drug classes to counter this threat. Antimicrobial peptides (AMPs) are potential candidates due to their membrane-disrupting mechanism of action. By specifically targeting fungal membranes and being rapidly fungicidal, they can reduce the chances of resistance development and treatment duration. Towards this goal, we conducted a head-to-head comparison of 61 short linear AMPs from the literature to identify the peptide with the most potent activity against fluconazole-resistant C. albicans. The 11-residue peptide, P11-6, was identified and assayed against a panel of clinical C. albicans isolates followed by fungicidal/static determination and a time-kill assay to gauge its potential for further drug development. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Siew Mei Samantha
authors.initials: SM
authors.lastname: Ng
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Yi Yong Alvin
authors.initials: YY
authors.lastname: Yap
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Jin Wei Darryl
authors.initials: JW
authors.lastname: Cheong
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Fui Mee
authors.initials: FM
authors.lastname: Ng
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Qiu Ying
authors.initials: QY
authors.lastname: Lau
authors.affiliation: Department of Laboratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433, Singapore.
authors.forename: Timothy
authors.initials: T
authors.lastname: Barkham
authors.affiliation: Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, 119074, Singapore.
authors.forename: Jeanette Woon Pei
authors.initials: JW
authors.lastname: Teo
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hill
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, 138669, Singapore.
authors.forename: Cheng San Brian
authors.identifier: http://orcid.org/0000-0002-1567-3983
authors.initials: CS
authors.lastname: Chia
mesh_terms: D000362:Agar; D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D002181:Candidiasis, Vulvovaginal / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D006801:Humans; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D023181:Antimicrobial Cationic Peptides; D008825:Miconazole; D015725:Fluconazole; D000362:Agar
keywords: Candida albicans; antifungal peptides; antimicrobial peptides; vulvovaginal candidiasis