Horizontal Gene Transfer: An Underestimated Driving Force for the Dissemination of Antibiotic Resistance Genes

Abstract

Antibiotic resistance (AMR) threatens the foundation of modern medicine, accelerated by horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs) among bacteria. This review examines HGT as the principal mechanism connecting immense ecological reservoirs of ARGs to clinical pathogens. The global “resistome” encompasses ancient ARGs in natural environments such as soil and water, which have intensified in human-impacted systems including wastewater treatment plants and gut microbiomes. The main molecular processes driving HGT—conjugation, transformation, and transduction—serve as key routes for ARG dissemination. Human activities, including antibiotic overuse, co-selection by heavy metals and biocides, and the generation of anthropogenic terrestrial hotspots, further promote resistance selection and increase gene transfer rates. Tackling AMR requires shifting from a 'clinical-pathogen-focused’ view to an ecological and evolutionary approach based on surveillance and management of gene flow at the human-animal-environment interface. Prospective approaches could concentrate on the direct disruption of HGT mechanisms and MGEs, as these could be considered as novel and more sustainable ways to mitigate the spreading of resistances.