Transcriptomic and Molecular Insights into the Response of Multidrug-Resistant Helicobacter pylori to Human Neutrophil Peptide 1 (HNP-1)

Multidrug-resistant (MDR) H. pylori infections present significant challenges in treatment, driving the need for novel therapeutic agents. Human neutrophil peptide 1 (HNP-1), an antimicrobial peptide, has shown potential activity against antibiotic-resistant pathogens, yet its specific efficacy and mechanisms against MDR H. pylori remain unexplored. The objective of this study was to evaluate the antibacterial activity of HNP-1 against multidrug-resistant (MDR) H. pylori. This study investigated the effects of HNP-1 on MDR H. pylori through a combination of in vitro and in silico approaches, including minimum inhibitory concentration (MIC) assays, molecular docking, and RNA sequencing. The MIC assay revealed that H. pylori strains exhibited high resistance to HNP-1 at 512 μg/mL, highlighting the need to understand this interaction at a molecular level. Molecular docking analysis identified key protein targets, RdxA, 23S rRNA, GyrA, and GyrB with varying binding affinities to HNP-1, suggesting potential pathways impacted by the peptide. RNA sequencing further revealed significant transcriptomic changes, with the ribosomal pathway and other metabolic pathways significantly upregulated upon treatment with HNP-1. These findings provide insights into H. pylori’s adaptive responses to HNP-1, enhance our understanding of its interactions with MDR H. pylori strains, and highlight pathways that may serve as future therapeutic targets, underscoring the need for continued research into AMPs as complementary therapeutic strategies.