Antibiotic Resistance and its Dissemination by Mobile Genetic Elements

Abstract

Antibiotics have been one of humankind's greatest discoveries. They have different modes of actions that can attack various bacterial components or mechanisms, including those that target cell wall or membrane, protein synthesis, nucleic acid synthesis, and metabolic pathways. Their implementation has paved the way for complicated and massive medical interventions and significantly decreased the morbidity and mortality rates caused by infectious diseases, thus prolonging human life span. However, this immense success has been undermined by a rising struggle against antibiotic resistance, which is a serious global threat to human health. Bacteria have responded to the antibiotic attack through several biochemical and genetic resistance mechanisms. This response is a prime example of bacteria's adaptation abilities and the pinnacle of evolution. Biochemical resistance mechanisms include limiting the antibiotic uptake, modifying the antibiotic target, inactivating the antibiotic, and active efflux of the antibiotic from the cell. Another major factor in developing antibiotic resistance is bacteria's ability to acquire pre-existing resistance genes from the bacterial genetic pool through mobile genetic elements capable of intracellular mobility within or between DNA molecules, including transposons, insertion sequences, and integrons, and those capable of intercellular mobility amongst bacterial cells including plasmids and integrative conjugative elements via horizontal gene transfer (conjugation, transformation, and transduction). Of all three major strategies, conjugation is thought to have the greatest effect on the dissemination of antibiotic resistance genes, whereas transduction and transformation are considered relatively less important in this context. Understanding the biochemical mechanisms and mobilisation of genetic elements are paramount to control the dissemination of these resistant genes.