title: Assessing the potential of four cathelicidins for the management of mouse candidiasis and Candida albicans biofilms.
abstract: As the most common fungal pathogen of humans, severe drug resistance has emerged in the clinically isolated Candida albicans, which lead to the urgency to develop novel antifungal agents. Here, four our previously characterized cathelicidins (cathelicidin-BF, Pc-CATH1, Cc-CATH2, Cc-CATH3) were selected and their antifungal activities against C. albicans were evaluated in vitro and in vivo using amphotericin B and LL-37 as control. Results showed that all four cathelicidins could eradicate standard and clinically isolated C. albicans strains with most MIC values ranging from 1 to 16 μg/ml, in less than 0.5 h revealed by time-kill kinetic assay. Four peptides only exhibited slight hemolytic activity with most HC50 > 200 μg/ml, and retained potent anti-C. albicans activity at salt concentrations below and beyond physiological level. In animal experiment, 50 mg/kg administration of the four cathelicidins could significantly reduce the fungal counts in a murine oral candidiasis model induced by clinically isolated C. albicans. The antibiofilm activity of cathelicidin-BF, the most potent among the five peptides was evaluated, and result showed that cathelicidin-BF strongly inhibited C. albicans biofilm formation at 20 μg/ml. Furthermore, cathelicidin-BF also exhibited potent anti-C. albicans activity in established biofilms as measured by metabolic and fluorescent viability assays. Structure-function analyses suggest that they mainly adopt an α-helical conformations, which enable them to act as a membrane-active molecule. Altogether, the four cathelicidins display great potential for antifungal agent development against candidiasis.
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China. Electronic address: yuhaining@dlut.edu.cn.
authors.forename: Haining
authors.initials: H
authors.lastname: Yu
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
authors.forename: Sijin
authors.initials: S
authors.lastname: Wu
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Marine Biological Technology, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Feng
authors.affiliation: College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215123, China. Electronic address: yipengwang@suda.edu.cn.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D054804:Cathelicidins / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D054804:Cathelicidins
keywords: Advanced structures; Anti-biofilm; Antifungal susceptibility; Cathelicidins; Oral candidiasis