title: A Designed Tryptophan- and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis.
abstract: New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV-NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs.
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Jin
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Bai
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Luan
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Yao
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology , Kunming 650223, Yunnan, China.|Joint Laboratory of Natural Peptide of University of Science and Technology of China and Kunming Institute of Zoology, Chinese Academy of Sciences , Kunming 650223, Yunnan, China.
authors.forename: Zhiye
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Liu
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Yan
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology , Kunming 650223, Yunnan, China.|Joint Laboratory of Natural Peptide of University of Science and Technology of China and Kunming Institute of Zoology, Chinese Academy of Sciences , Kunming 650223, Yunnan, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Rong
authors.affiliation: Life Sciences College of Nanjing Agricultural University , Nanjing 210095, Jiangsu, China.|Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology , Kunming 650223, Yunnan, China.|Joint Laboratory of Natural Peptide of University of Science and Technology of China and Kunming Institute of Zoology, Chinese Academy of Sciences , Kunming 650223, Yunnan, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology , Kunming 650223, Yunnan, China.|Joint Laboratory of Natural Peptide of University of Science and Technology of China and Kunming Institute of Zoology, Chinese Academy of Sciences , Kunming 650223, Yunnan, China.
authors.forename: Qiumin
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001120:Arginine / Q000032:analysis / Q000737:chemistry; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D025141:Drug Resistance, Fungal / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008239:Lysine / Q000032:analysis / Q000737:chemistry; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000032:analysis / Q000737:chemistry; D014627:Vaginitis / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D014364:Tryptophan; D001120:Arginine; D008239:Lysine