Abstract
Helicobacter pylori (H. pylori) infection is prevalent all over the world, which may even cause gastric cancer. Unfortunately, current antibiotic therapy cannot completely eradicate drug-resistant H. pylori. HF-18 (GFFKKAWRKVKKAFRRVL-NH2), a novel cationic antimicrobial peptide, showed broad antimicrobial activities, low cytotoxicity toward mammalian cells and low drug tolerance during our previous research. In this paper, to investigate the antibacterial activities and possible mechanisms underlying HF-18 against drug-resistant H. pylori, cytotoxin associated protein (CagA)-carrying recombinant E. coli BL21 was constructed. Subsequently, Zeta potential detection, N-Phenyl-1-naphthylamine uptake, propidium iodide fluorescence uptake, transmission electron microscope, qRT-PCR and Western blot assays were performed. Consequently, we found that HF-18 had potent antibacterial effects on clarithromycin- and amoxicillin- resistant H. pylori. In terms of its mode of action, HF-18 could neutralize negative charges on the surface of H. pylori, penetrate into and disrupt the integrity of bacterial membranes, resulting in the death of drug-resistant H. pylori to reduce cells infection. In addition, HF-18 inhibited the transcription of adhesion gene alpA/alpB and the expression of virulence protein CagA under sub-inhibitory concentration, and ultimately decreased bacterial virulence. Therefore, HF-18 lays a foundation for the development and utilization of new antibiotics.
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Abbreviations
- CFU:
-
Colony forming unit
- Glu:
-
Glutamic acid
- Lys:
-
Lysine
- IPTG:
-
Isopropyl β-d-1-thiogalactopyranoside
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Acknowledgements
This work was funded by the National Natural Science Foundation of China (Grant No. 82173863; No.81803591); National Key Research and Development Program of China (Grant No. 2018YFA0902000); the fellowship of China postdoctoral science foundation (Grant No. 2020T130723); Natural Science Foundation of Jiangsu Province of China (Grant No. BK20201327); the Basic Scientific Research Business Expense Project of China Pharmaceutical University (Grant No. 2632021ZD07)
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Zhou, C., Jiang, M., Ye, X. et al. Antibacterial Activities of Peptide HF-18 Against Helicobacter pylori and its Virulence Protein CagA. Int J Pept Res Ther 28, 63 (2022). https://doi.org/10.1007/s10989-022-10372-7
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DOI: https://doi.org/10.1007/s10989-022-10372-7