Md Nesran Zarith Nameyrra, Hanafiah Alfizah, Sukri Asif, Mohd Fahami Nur Azlina, Raja Ali Raja Affendi, Lopes Bruno Silvester
Dept. of Medical Microbiology & Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000, Cheras, Kuala Lumpur, Malaysia.
GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000, Cheras, Kuala Lumpur, Malaysia.
Probiotics Antimicrob Proteins. 2025 Sep 12. doi: 10.1007/s12602-025-10747-4.
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.
多重耐药（MDR）幽门螺杆菌感染在治疗中带来了重大挑战，这推动了对新型治疗药物的需求。人中性粒细胞肽1（HNP-1）是一种抗菌肽，已显示出对耐抗生素病原体的潜在活性，但其针对多重耐药幽门螺杆菌的具体疗效和机制仍未得到探索。本研究的目的是评估HNP-1对多重耐药（MDR）幽门螺杆菌的抗菌活性。本研究通过体外和计算机模拟相结合的方法，包括最低抑菌浓度（MIC）测定、分子对接和RNA测序，研究了HNP-1对多重耐药幽门螺杆菌的影响。MIC测定显示，幽门螺杆菌菌株对512μg/mL的HNP-1表现出高抗性，这突出了在分子水平上理解这种相互作用的必要性。分子对接分析确定了关键蛋白质靶点，即RdxA、23S rRNA、GyrA和GyrB，它们与HNP-1具有不同的结合亲和力，表明该肽可能影响的潜在途径。RNA测序进一步揭示了显著的转录组变化，在用HNP-1处理后，核糖体途径和其他代谢途径显著上调。这些发现为幽门螺杆菌对HNP-1的适应性反应提供了见解，增强了我们对其与多重耐药幽门螺杆菌菌株相互作用的理解，并突出了可能作为未来治疗靶点的途径，强调了继续研究抗菌肽作为补充治疗策略的必要性。
