title: Activity of Novel Synthetic Peptides against Candida albicans.
abstract: Candida spp. are the most common causes of fungal infections worldwide. Among the Candida species, Candida albicans remains the predominant species that causes invasive candidiasis in most countries. In this study, we used two peptides, KABT-AMP and uperin 3.6 as templates to develop novel antifungal peptides. Their anticandidal activity was assessed using a combination of MIC, time-killing assay and biofilm reduction assay. Hybrid peptides, KU2 and KU3 containing a mixed backbone of KABT-AMP and Uperin 3.6 demonstrated the most potent anticandidal activity with MIC values ranging from 8-16 mg/L. The number of Trp residues and the amphipathic structure of peptides probably enhanced the anticandidal activity of peptides. Increasing the cationicity of the uperin 3.6 analogues resulted in reduced MIC from the range of 64-128 mg/L to 16-64 mg/L and this was also correlated with the antibiofilm activity and killing kinetics of the peptides. Peptides showed synergistic effects when used in combination with conventional antifungals. Peptides demonstrated low haemolytic activity but significant toxicity on two normal human epithelial cell lines. This study provides us with a better understanding on the structure-activity relationship and the balance between cationicity and hydrophobicity of the peptides although the therapeutic application of the peptides is limited.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kah Yean
authors.initials: KY
authors.lastname: Lum
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Sun Tee
authors.initials: ST
authors.lastname: Tay
authors.affiliation: School of Pharmacy, Faculty of Science, University Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia.
authors.forename: Cheng Foh
authors.initials: CF
authors.lastname: Le
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur.
authors.forename: Vannajan Sanghiran
authors.initials: VS
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur.
authors.forename: Nadia Hanim
authors.initials: NH
authors.lastname: Sabri
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rukumani Devi
authors.initials: RD
authors.lastname: Velayuthan
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Hamimah
authors.initials: H
authors.lastname: Hassan
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Shamala Devi
authors.initials: SD
authors.lastname: Sekaran
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000254:growth & development*; D002177:Candidiasis / Q000188:drug therapy*; D006801:Humans; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D010455:Peptides