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Antibacterial activity and dual mechanisms of peptide analog derived from cell-penetrating peptide against Salmonella typhimurium and Streptococcus pyogenes

  • Applied Microbial and Cell Physiology
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Abstract

A number of research have proven that antimicrobial peptides are of greatest potential as a new class of antibiotics. Antimicrobial peptides and cell-penetrating peptides share some similar structure characteristics. In our study, a new peptide analog, APP (GLARALTRLLRQLTRQLTRA) from the cell-penetrating peptide ppTG20 (GLFRALLRLLRSLWRLLLRA), was identified simultaneously with the antibacterial mechanism of APP against Salmonella typhimurium and Streptococcus pyogenes. APP displayed potent antibacterial activity against Gram-negative and Gram-positive strains. The minimum inhibitory concentration was in the range of 2 to 4 μM. APP displayed higher cell selectivity (about 42-fold increase) as compared to the parent peptide for it decreased hemolytic activity and increased antimicrobial activity. The calcein leakage from egg yolk l-α-phosphatidylcholine (EYPC)/egg yolk l-α-phosphatidyl-dl-glycerol and EYPC/cholesterol vesicles demonstrated that APP exhibited high selectivity. The antibacterial mechanism analysis indicated that APP induced membrane permeabilization in a kinetic manner for membrane lesions allowing O-nitrophenyl-β-d-galactoside uptake into cells and potassium release from APP-treated cells. Flow cytometry analysis demonstrated that APP induced bacterial live cell membrane damage. Circular dichroism, fluorescence spectra, and gel retardation analysis confirmed that APP interacted with DNA and intercalated into the DNA base pairs after penetrating the cell membrane. Cell cycle assay showed that APP affected DNA synthesis in the cell. Our results suggested that peptides derived from the cell-penetrating peptide have the potential for antimicrobial agent development, and APP exerts its antibacterial activity by damaging bacterial cell membranes and binding to bacterial DNA to inhibit cellular functions, ultimately leading to cell death.

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Acknowledgments

This research was funded by the National Natural Science Foundation of China (grant nos. 30871805 and 31172214).

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Authors and Affiliations

  1. The State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, China

    Lirong Li, YongHui Shi, GuanFang Su & GuoWei Le

  2. Institute of Food Nutrition and Safety, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu Province, China

    Lirong Li, YongHui Shi, Maureen Jepkorir Cheserek, GuanFang Su & GuoWei Le

  3. Human Nutrition Department, Egerton University, PO BOX 536, Egerton, Kenya

    Maureen Jepkorir Cheserek

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  1. Lirong Li
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  2. YongHui Shi
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  3. Maureen Jepkorir Cheserek
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  4. GuanFang Su
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  5. GuoWei Le
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Correspondence to GuoWei Le.

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Li, L., Shi, Y., Cheserek, M.J. et al. Antibacterial activity and dual mechanisms of peptide analog derived from cell-penetrating peptide against Salmonella typhimurium and Streptococcus pyogenes . Appl Microbiol Biotechnol 97, 1711–1723 (2013). https://doi.org/10.1007/s00253-012-4352-1

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  • DOI: https://doi.org/10.1007/s00253-012-4352-1

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