Mechanism of antifungal activity of antimicrobial peptide APP, a cell-penetrating peptide derivative, against Candida albicans: intracellular DNA binding and cell cycle arrest

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• 作者：Lirong Li ; Jin Sun ; Shufang Xia ; Xu Tian…
• 关键词：Candida albican ; Antifungal ; Antimicrobial peptide ; DNA binding ; Cell cycle
• 刊名：Applied Microbiology and Biotechnology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：100
• 期：7
• 页码：3245-3253
• 全文大小：1,246 KB
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• 作者单位：Lirong Li (1) (2)
  Jin Sun (1)
  Shufang Xia (1)
  Xu Tian (1)
  Maureen Jepkorir Cheserek (3)
  Guowei Le (1)
  
  1. Institute of Food Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu Province, China
  2. Yunnan Institute of Food Safety, Kunming University of Science and Technology, Kunming, Yunnan Province, China
  3. Human Nutrition Department, Egerton University, PO BOX 536, Egerton, Kenya
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Biotechnology
  Microbiology
  Microbial Genetics and Genomics
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0614

文摘

We investigated the antifungal properties and anti-candidal mechanism of antimicrobial peptide APP. The minimum inhibitory concentration of APP was 8 μM against Candida albicans and Aspeogillus flavus, the concentration against Saccharomyces cerevisiae and Cryptococcus neoformans was 16 μM, while 32 μM inhibited Aspergilla niger and Trichopyton rubrum. APP caused slight depolarization (12.32 ± 0.87 %) of the membrane potential of intact C. albicans cells when it exerted its anti-candidal activity and only caused 21.52 ± 0.48 % C. albicans cell membrane damage. APP interacted with cell wall membrane, caused potassium efflux and nucleotide leakage. However, confocal fluorescence microscopy experiment and flow cytometry confirmed that FITC-labeled APP penetrated C. albicans cell membrane with 52.31 ± 1.88 % cell-penetrating efficiency and accumulated in the cytoplasm. Then, APP interact with C. albicans genomic DNA and completely suppressed DNA migration above weight ratio (peptide/DNA) of 2, and significantly arrested cell cycles during the S-phase (S-phase cell population was 27.09 ± 0.73 %, p < 0.05) after penetrating the cell membrane. Results indicated that APP kills C. albicans for efficient cell-penetrating efficiency, strong DNA-binding affinity and significant physiological changes inducing S-phase arrest in intracellular environment.