RESUMEN
The SOS DNA repair system is induced in bacteria treated with 4-quinolones. However, whether the response exacerbates or repairs the damage caused by these drugs is still unclear. The recA13 and the recB21 mutations impair recombination repair and render bacteria unable to induce the SOS response when treated with nalidixic acid or other agents that affect DNA synthesis. However, UV treatment induces the SOS response in recB21 mutants but not in recA13 mutants. Both these mutants are hypersensitive to nalidixic acid and, therefore, either recombination repair or SOS repair would appear to repair DNA damage caused by the drug. However, since the lexA3 mutation (which also renders bacteria incapable of inducing the SOS response without affecting recombination repair) had no effect on the susceptibility of bacteria to nalidixic acid, the SOS response neither contributes to nor repairs DNA damage caused by the drug. Consequently, it would seem that the hypersensitivity of the recA13 and recB21 mutants to nalidixic acid is due to their deficiency in recombination repair. This view was confirmed by testing a recA430 mutant that is recombination-repair proficient but SOS repair-deficient and finding it to be no more sensitive to nalidixic acid than its parent. Thus it would appear that, although induced by nalidixic acid treatment, the SOS DNA repair system does not play any role in bacterial responses to the damage caused by the drug. In contrast, the recombination repair system does repair damage caused by nalidixic acid.
Asunto(s)
Antiinfecciosos/farmacología , Reparación del ADN , Escherichia coli/efectos de los fármacos , Ácido Nalidíxico/farmacología , Respuesta SOS en Genética , Serina Endopeptidasas , Proteínas Bacterianas/genética , Daño del ADN , Reparación del ADN/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Exodesoxirribonucleasa V , Exodesoxirribonucleasas/genética , Mutación , Rec A Recombinasas/genética , Recombinación Genética , Respuesta SOS en Genética/efectos de los fármacosRESUMEN
The activity of ten different 4-quinolone antibacterial agents against Escherichia coli KL16 was investigated at four pH values between 5.6 and 8.3, which is the pH range of urine. It was found that pH affected the minimum inhibitory concentrations of all the drugs, but the nature of the substituent at the C7 position of each 4-quinolone governed how its activity was altered by the hydrogen ion concentration. When a 4-quinolone possessed a piperazine group at its C7 position its activity became progressively less as the pH fell. However, all drugs that lacked a C7 piperazine, irrespective of the nature of their substituent at this position, exhibited a progressive increase in activity as the pH was reduced. In addition it was found that, excepting cinoxacin, a urinary concentration of magnesium generally caused a further antagonism of the activity of the nine other 4-quinolone antibacterials at all pH values tested.