Recent Insights into Tackling Multidrug Resistance in Gram-Negative Bacterial Pathogens

Gram-negative bacteria, notorious for their intrinsic and acquired resistance mechanisms, pose a significant threat to public health. The emergence of multidrug-resistant (MDR) strains, particularly among common pathogens like E. coli and Klebsiella pneumoniae, has severely limited treatment options. Recent research is revealing new aspects of Gram-negative resistance, offering useful insights for public health and clinical practice.Their resistance relies on features such as a tough outer membrane that blocks drug entry, active efflux pumps that remove antibiotics, and the rapid spread of resistance genes through horizontal gene transfer. Mobile genetic elements—plasmids, integrons, and transposons—help these genes move within and between bacterial populations. Biofilms and community interactions further protect cells and promote resistance.Work using metagenomics, genomics, proteomics, and other molecular tools has revealed how resistance genes arise, are regulated, and spread in different environments. Antibiotic use can select for resistance across whole microbial communities, not only in the target pathogen, underscoring the need for careful antibiotic use and monitoring.Researchers are dissecting the structure and function of outer membrane porins, characterizing efflux pump systems, and mapping regulatory networks that control resistance. They are also exploring how biofilms, phage–bacteria interactions, and community structure shape resistance patterns and host adaptation. New strategies aim to disrupt these defences, including membrane-permeabilizing agents, efflux pump inhibitors, small molecules that target resistance pathways, bacteriophages, and phage-derived enzymes.These advances have clear implications for practice and policy. In public health, the One Health framework—which links human, animal, and environmental health—guides resistance surveillance across sectors and supports stricter control of antibiotic use in healthcare and agriculture. For clinicians, rapid diagnostics that detect specific resistance mechanisms can guide targeted therapy and reduce broad-spectrum use. Alternative treatments, such as bacteriophages and antimicrobial peptides, are also being evaluated.This Research Topic focuses on deepening our understanding of multidrug resistance in Gram-negative bacteria and turning that knowledge into better interventions. We invite contributions that address, among other themes:- Outer membrane structure and permeability changes that affect antibiotic entry- Structure, regulation, and inhibition of efflux pumps- Mechanisms and regulation of horizontal gene transfer (plasmids, transposons, integrons)- Molecular links between biofilm formation and resistance- Phage–bacteria interactions, including phage resistance, CRISPR-Cas, and phage-based therapies- Regulatory networks controlling intrinsic and acquired resistance- Molecular targets for combination treatments and membrane-permeabilizing strategies- Connections between resistance mechanisms, virulence, and host adaptationWe welcome Original Research, Reviews, Mini-Reviews, Brief Research Reports, and Perspectives that clarify the molecular basis of Gram-negative multidrug resistance and support new ways to prevent and treat these infections. Topic editors: Chaitanya Tellapragada, Arunagirinathan Narasingam, Rameshkumar Marimuthu Ragavan Source: https://www.frontiersin.org/research-topics/76074/recent-insights-into-tackling-multidrug-resistance-in-gram-negative-bacterial-pathogens