Antibiotic Resistance of Bacterial Agents of Disease

The prevalence of increased antibiotic resistance of bacterial agents of disease is a serious clinical concern because it limits and reduces the efficiency of the treatment options that are available. The mechanism of the development of antibiotic resistance has been attributed to bacteria’s capacity to mutate. The mutation alters existing resistance determinants to antimicrobial agents and produces different drug targets that have decreased antibiotic affinity. Thus, mutators that have high mutation frequencies could have important roles in developing antibiotic resistance (Chopra, O’Neill, &amp. Miller, 2003). It is believed that bacteria mutate as part of its endogenous survival mechanism. In E. coli, defects in genes in pathways that are involved in DNA repair and error correction systems, and prevention of incorporation of oxidized guanines, lead to the development of permanent mutator phenotypes (Miller, ONeill, &amp. Chopra, 2002). High frequencies of mutations can be toxic to bacterial cultures but there are reports of naturally occurring organisms that have 1000-fold greater than normal mutation frequencies.
Agents that can damage the DNA include ionizing radiation and reactive oxygen species that cause strand breaks and removal of amine and purine groups in the DNA. Oxidation also produces 2’-deoxy-7, 8-dihydro-8-oxoguanosine, (or 8-oxo-dG) from guanine. 8-oxo-dG will pair with adenine which resulting in transversion (Shibutani, Takeshita, &amp. Grollman, 1991). MutT, MutM, and MutY are bacterial enzymes that eliminate 8-oxo-dG or reduce its effects. Of the three enzymes, it is the loss of mutT activity that has the largest effect on increasing mutational frequencies (Miller J., 1996).