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Antimicrobial Activities of Peptide Cbf-K(16) against Drug-Resistant Helicobacter Pylori Infection in Vitro and in Vivo
SUNLONG BIOTECH / 2024-01-09
  • Author:Jiang, M., Ma, L., Huang, Y., Wu, H., Dou, J. & Zhou, C.

  • Periodical:Microbial pathogenesis 138, 103847 (2020)

  • Article source

Helicobacter pylori (H. pylori) infection is highly prevalent, and has developed antimicrobial resistance to virtually all existing antibiotics. Currently, treatment of H. pylori infection (involving proton pump inhibitors and broad-spectrum antibiotics) is suboptimal, with high failure rates. Thus, there is a pressing need to develop new anti-H. pylori therapies. Cbf-K(16), a cathelicidin-like antimicrobial peptide, presented broad antimicrobial activity during our previous research. This study further evaluated the therapeutic potential and the mode of action underlying Cbf-K(16) against clarithromycin- and amoxicillin-resistant H. pylori SS1. The MIC and MBC of Cbf-K(16) against the tested H. pylori were 16 and 32?μg/ml, respectively, and its killing kinetics was time-dependent, reflecting the thorough elimination of drug-resistant bacteria within 24?h. This peptide also protected H. pylori-infected gastric epithelial cells (GES-1) from death by reducing the cell supernatant and intracellular bacterial counts by 1.9 and 2.9-log(10) units, respectively. These data indicated the powerful antimicrobial effects of Cbf-K(16)in vitro. Meanwhile, notable antimicrobial activity in the mouse gastritis model was observed, with decreasing bacterial counts by 3.9-log(10) units in stomach tissues and Cbf-K(16) could effectively suppress the secretion of inflammatory cytokine IL-8. For its mode of action, Cbf-K(16) not only neutralized the negative potential and increased the membrane uptake of NPN and PI by 78.5% and 85.1%, respectively, but also bound to genomic DNA, which in turn downregulated the expression of adhesion genes (alpA and alpB) and virulence gene (cagA), indicating its effective activities on membrane disruption, DNA-binding and gene expression. The data above demonstrated that Cbf-K(16) possessed effective antimicrobial and anti-inflammatory activities and downregulated the expression of adhesion- and cytotoxin-associated genes of drug-resistant H. pylori SS1, making it a potential candidate for anti-infective therapy.

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