Antimicrobial activities of peptide Cbf-K16 against drug-resistant Helicobacter pylori infection in vitro and in vivo. (January 2020)

• Record Type: Journal Article
• Authors: Jiang, Meiling; Ma, Lingman; Huang, Ya; Wu, Haomin; Dou, Jie; Zhou, Changlin
• Is Part Of: Microbial pathogenesis. Volume 138(2020)
• Publication Date: 2020-01
• Subjects: Cbf-K16 -- Antimicrobial activity -- Drug-resistant -- H. pylori -- Anti-inflammatory activity; CFU Colony forming unit -- TEM Transmission electron microscopy -- NPN N-Phenyl-1-naphthylamine -- PI Propidium iodide -- FITC Fluorescein isothiocyanate -- DAPI 4, 6-diamidino-2-phenylindoleAbstract; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2019.103847
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: 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-K16, 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-K16 against clarithromycin- and amoxicillin-resistant H. pylori SS1. The MIC and MBC of Cbf-K16 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-log10 units, respectively. These data indicated the powerful antimicrobial effects of Cbf-K16 in vitro . Meanwhile, notable antimicrobial activity in the mouse gastritis model was observed, with decreasing bacterial counts by 3.9-log10 units in stomach tissues and Cbf-K16 could effectively suppress the secretion of inflammatory cytokine IL-8. For its mode of action, Cbf-K16 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-K16 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. Highlights: The antimicrobial effect of Cbf-K16 against drug-resistant H. pylori is significant. Cbf-K16 exerts antimicrobial activity by membrane disruption and DNA-binding. The adhesion- and cytotoxin-related gene expression can be downregulated by Cbf-K16 . Drug-resistant H. pylori SS1 induced gastritis can be improved by Cbf-K16 .