Multidrug resistance in bacteria arises through two main mechanisms: the accumulation of resistance genes on plasmids or transposons, and the increased expression of multidrug efflux pumps. Resistance genes can be transferred between bacteria via plasmids, and many of these genes originate from antibiotic-producing organisms or environmental bacteria. Resistance mechanisms include target modification, enzymatic inactivation of the drug, and preventing drug access to the target. Efflux pumps, such as those in the Major Facilitator Superfamily (MFS) and Resistance-Nodulation-Division (RND) families, actively expel drugs from the cell. RND pumps are particularly important in gram-negative bacteria, as they work synergistically with the outer membrane barrier to expel drugs. These pumps are often regulated by repressor proteins and can be induced by the presence of specific substrates. The structure and function of RND pumps, including their periplasmic and transmembrane domains, have been studied extensively, revealing their role in multidrug resistance. The assembly and transfer of resistance genes are facilitated by plasmids and transposons, which can be transferred between bacteria through conjugation. Understanding these mechanisms is crucial for developing strategies to combat multidrug-resistant bacterial infections.Multidrug resistance in bacteria arises through two main mechanisms: the accumulation of resistance genes on plasmids or transposons, and the increased expression of multidrug efflux pumps. Resistance genes can be transferred between bacteria via plasmids, and many of these genes originate from antibiotic-producing organisms or environmental bacteria. Resistance mechanisms include target modification, enzymatic inactivation of the drug, and preventing drug access to the target. Efflux pumps, such as those in the Major Facilitator Superfamily (MFS) and Resistance-Nodulation-Division (RND) families, actively expel drugs from the cell. RND pumps are particularly important in gram-negative bacteria, as they work synergistically with the outer membrane barrier to expel drugs. These pumps are often regulated by repressor proteins and can be induced by the presence of specific substrates. The structure and function of RND pumps, including their periplasmic and transmembrane domains, have been studied extensively, revealing their role in multidrug resistance. The assembly and transfer of resistance genes are facilitated by plasmids and transposons, which can be transferred between bacteria through conjugation. Understanding these mechanisms is crucial for developing strategies to combat multidrug-resistant bacterial infections.