Affiliation:
1. Department of Life Science, Dongguk University-Seoul, Goyang 10326, Republic of Korea
2. Species Diversity Research Division, National Institute of Biological Resources, Incheon 22689, Republic of Korea
Abstract
The escalating prevalence of antibiotic-resistant bacteria poses an immediate and grave threat to public health. Antimicrobial peptides (AMPs) have gained significant attention as a promising alternative to conventional antibiotics. Animal venom comprises a diverse array of bioactive compounds, which can be a rich source for identifying new functional peptides. In this study, we identified a toxin peptide, Lycotoxin-Pa1a (Lytx-Pa1a), from the transcriptome of the Pardosa astrigera spider venom gland. To enhance its functional properties, we employed an in silico approach to design a novel hybrid peptide, KFH-Pa1a, by predicting antibacterial and cytotoxic functionalities and incorporating the amino-terminal Cu(II)- and Ni(II) (ATCUN)-binding motif. KFH-Pa1a demonstrated markedly superior antimicrobial efficacy against pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, compared to Lytx-Pa1a. Notably, KFH-Pa1a exerted several distinct mechanisms, including the disruption of the bacterial cytoplasmic membrane, the generation of intracellular ROS, and the cleavage and inhibition of bacterial DNA. Additionally, the hybrid peptide showed synergistic activity when combined with conventional antibiotics. Our research not only identified a novel toxin peptide from spider venom but demonstrated in silico-based design of hybrid AMP with strong antimicrobial activity that can contribute to combating MDR pathogens, broadening the utilization of biological resources by incorporating computational approaches.
Funder
Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education
National Institute of Biological Resources (NIBR), funded by the Ministry of Environment (MOE) of the Republic of Korea
Subject
Health, Toxicology and Mutagenesis,Toxicology
Reference55 articles.
1. Antibiotics: Past, present and future;Hutchings;Curr. Opin. Microbiol.,2019
2. The past, present, and future of antibiotics;Cook;Sci. Transl. Med.,2022
3. How antibiotics kill bacteria: From targets to networks;Kohanski;Nat. Rev. Microbiol.,2010
4. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis;Tacconelli;Lancet Infect. Dis.,2018
5. Terreni, M., Taccani, M., and Pregnolato, M. (2021). New Antibiotics for Multidrug-Resistant Bacterial Strains: Latest Research Developments and Future Perspectives. Molecules, 26.