Targeting Horizontal Gene Transfer to Combat Antimicrobial Resistance: A Review of Mechanisms, Drivers, and Multi-Omics Strategies

Lili Tang,1 Wei Yang,1 Lingqi Yang,1 You Lv,2 Jian Zhang1 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Information Center of West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Jian Zhang, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email [email protected]: The widespread dissemination of antibiotic resistance genes in bacteria primarily relies on horizontal gene transfer (HGT), a phenomenon that has profound implications for global healthcare and animal husbandry. Therefore, elucidating the key mechanisms of HGT is crucial for controlling the global spread of resistance genes. Horizontal gene transfer can occur not only through classical pathways such as conjugation, transformation, and transduction but also involves non-classical mechanisms including gene transfer agents, outer membrane vesicles, and nanotubes. This process is mediated by various mobile genetic elements, such as plasmids, bacteriophages, transposons, integrons, integrative and conjugative elements (ICEs), and integrative and mobilizable elements (IMEs). HGT is typically regulated by a combination of host-specific intrinsic factors and external environmental conditions. To address the spread of resistance, numerous detection and prevention tools targeting this mechanism have been developed. This article focuses on the process of HGT and its associated mobile genetic elements, systematically analyzes key factors influencing this process, summarizes sequencing and bioinformatic technologies used for monitoring HGT, and explores prevention strategies informed by genomic, proteomic, and metabolomic approaches. The aim is to provide a theoretical foundation and practical guidance for the control of drug-resistant bacteria.Keywords: HGT, ARGs, MGEs, control of drug-resistant bacteria