Mechanisms and Spread of Bacterial Resistance to Antimicrobial Agents

Nowadays, antimicrobial agents are among the most frequently used therapeutics in human and veterinary medicine. Resistance to antimicrobial agents can be subdivided into two basic types of resistance, intrinsic resistance and acquired resistance. Resistance to ß-lactam antibiotics is mainly due to inactivation by ß-lactamases and decreased ability to bind to penicillin-binding proteins (PBPs) in both gram-positive and gram-negative bacteria, but may also be based on decreased uptake of ß-lactams due to permeability barriers or increased efflux via multidrug transporter systems. Different types of multidrug transporters mediating resistance to tetracycline in addition to resistance to a number of structurally unrelated compounds are described, for instance, in Escherichia coli, Salmonella, and P. aeruginosa. Plasmids, genomic islands, transposons, gene cassettes, and integrons are spread vertically during the division of the host cell, but can also be transferred horizontally between bacteria of the same or different species and genera via transduction, conjugation and mobilization, or transformation. The development of antimicrobial resistance—by either mutations, generation of new resistance genes, or acquisition of resistance genes already present in other bacteria—is a complex process that involves different mechanisms. Due to the usage of all types of antimicrobial substances for selection of resistant bacteria, prudent use of the antimicrobial agents is strongly recommended in both human and veterinary medicine, as well as in food animal production, to retain the efficacy of antimicrobial agents for the control of bacterial infections in animals.