A Detailed Review of Horizontal Gene Transfer as a Cause of Antibiotic Resistance: Environmental Vectors, Experimental Strategies for Intervention, and Molecular Mechanisms
DOI:
https://doi.org/10.32350/cpr.41.04Keywords:
antimicrobial resistance, antibiotic resistance genes, CRISPR-Cas9, conjugation, mobile genetic elements, one health, transformation, transductionAbstract
Horizontal Gene Transfer or HGT is an important mechanism leading to the global spread of antibiotic resistance, enabling bacteria to gain and share resistance determinants across taxonomic boundaries in environmental, clinical, and agricultural settings. This thorough analysis compares the corresponding contributions of the three main HGT pathways—conjugation, transformation, and transduction—to the spread of antimicrobial resistance (AMR) in terms of DNA transfer capacity, host range, and clinical frequency. Conjugation is the prominent mechanism in the clinical environment which is responsible for the inter-species dissemination of crucial resistance determinants, including mcr-1 (mobilized colistin resistance), blaNDM-1 (New Delhi metallo-β-lactamase-1], and blaKPC (Klebsiella pneumoniae carbapenemase), primarily via incompatibility group IncI2, IncX3, and IncF plasmids. Environmental storages—including wastewater treatment plants (WWTPs), manure-amended agricultural soils, and hospital biofilms—function as critical hotspots for antibiotic resistance gene (ARG) amplification and inter-kingdom gene exchange, where selective pressures from antibiotics, heavy metals, and biocides accelerates horizontal gene transfer and the evolution of multidrug-resistant microorganisms. Pakistan is nominated as an increased-risk region where the merging of inadequate diagnostic infrastructure, unregulated OTC antibiotic access, and poor wastewater management makes the environment that markedly speeds up HGT-mediated resistance. Innovative molecular intervention approaches, including DNase-functionalized nanocarriers, CRISPR-Cas9-based plasmid curing, and engineered bacteriophages, demonstrate significant preclinical promise but face extensive translational hurdles to clinical stationing. This study accentuates the requirement for a unified One Health strategy — coordinating veterinary, human, and environmental health policy — alongside evidence-based antibiotic stewardship, enhanced wastewater management, and molecular surveillance to curb the ongoing AMR crisis driven by HGT.
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