Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle against .

La-Mei Zhang, Sheng-Wen Zhou, Xiao-Shan Huang, Yi-Fan Chen, James Mwangi, Ya-Qun Fang, Ting Du, Min Zhao, Lei Shi, Qiu-Min Lu
Author Information
  1. La-Mei Zhang: Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming 650224, China.
  2. Sheng-Wen Zhou: Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China.
  3. Xiao-Shan Huang: Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China.
  4. Yi-Fan Chen: Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China.
  5. James Mwangi: Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China.
  6. Ya-Qun Fang: Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China.
  7. Ting Du: Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming 650224, China.
  8. Min Zhao: Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming 650224, China. ORCID
  9. Lei Shi: Institute of Highland Forest Science, Chinese Academy of Forestry, Kunming 650224, China.
  10. Qiu-Min Lu: Engineering Laboratory of Peptides of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Key Laboratory of Genetic Evolution & Animal Models, Sino-African Joint Research Center, and New Cornerstone Science Laboratory, Kunming Institute of Zoology, the Chinese Academy of Sciences, No.17 Longxin Road, Kunming 650201, China. ORCID

Abstract

() is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of (), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against , with a minimum inhibitory concentration (MIC) of 0.81 ��M. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by .

Keywords

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Grants

  1. 202302AE090017, 202302AE090009, 202001AT070128, 202003AD150008 and 202302AA310035/Yunnan Provincial Science and Technology Department
  2. JiaoWaiSiYa[2020]619#/Lancang-Mekong Cooperation Special Fund Projects
  3. 2023YFF1304904, 2022YFC2105003/National Key Research and Development Program of China
  4. 31930015, 32002311 and U2002219/the National Natural Science Foundation of China
  5. 2019]50#/National Forestry Science and Technology Promotion Project
  6. 2022SCP007/Kunming Science and Technology Bureau
  7. NCI202238/New Cornerstone Investigator Program from Shenzhen New Cornerstone Science Foundation
  8. 2022YKZY006/the Yunnan Characteristic Plant Extraction Laboratory
  9. TFJC2023010007/Tianfu Jincheng Laboratory Foundation

MeSH Term

Cryptococcus neoformans
Animals
Antifungal Agents
Microbial Sensitivity Tests
Coleoptera
Antimicrobial Peptides
Humans
Biofilms
Amino Acid Sequence

Chemicals

Antifungal Agents
Antimicrobial Peptides

Word Cloud

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