The synergistic role of efflux pumps and biofilm in Helicobacter pylori antibiotic resistance: a narrative review

Multidrug resistance in Helicobacter pylori has reached alarming levels, compromising standard eradication therapies worldwide. This narrative review examines the interaction between efflux pumps and biofilm formation as key factors driving multidrug resistance (MDR) in this pathogen. A systematic search of databases (PubMed, ResearchGate, Google Scholar, Web of Science, and Scopus) was conducted to identify relevant literature, and findings were synthesized narratively. Efflux pumps belonging to resistance–nodulation–division (RND), the major facilitator superfamily (MFS), the ATP-binding cassette (ABC) superfamily, the multidrug and toxic compound extrusion (MATE) family, and the small multidrug resistance (SMR) family actively expel antibiotics and reduce intracellular drug concentrations. Concurrently, biofilms create a protective matrix that restricts drug penetration and harbors persister cells. Emerging evidence indicates that efflux pumps not only confer resistance but also support biofilm architecture, stress adaptation, and bacterial survival in the gastric environment. Based on the recent in vitro, in vivo, and clinical studies, we explore key molecular mechanisms, including efflux gene upregulation during biofilm development and regulatory control by SpoT-mediated stringent responses. We also discuss therapeutic strategies targeting this interaction, such as efflux pump inhibitors, biofilm disruptors, natural compounds, and nanoparticle-based delivery systems. Understanding this dynamic collaboration is essential for developing novel strategies to revitalize the eradication of H. pylori and reduce associated disease burdens.