Efeito de concentração sub-inibitóra de piperacilina-tazobactam na morfologia e fisiologia de Escherichia coli

Abstract

E. coli is one of the most common inhabitants of the intestinal tract and, although it is not necessarily pathogenic, it is a facultative anaerobic bacterium that is most frequently isolated from intra-abdominal infections. The combination of piperacillintazobactam (PTZ) is among the antimicrobial drugs that can be used for the treatment of polymicrobial infections in which E. coli is often involved. During antimicrobial therapy, inhibitory concentrations of drugs used are always followed by sub-inhibitory concentrations. It has been shown that drugs in sub-MIC(concentrations below the minimum inhibitory concentration) influence the phenotypic properties of bacteria, especially the induction of filamentous cells, whose degree of aggressiveness is not consensual. In this work, we evaluated the effect of half minimum inhibitory concentration of PTZ (0.5 x MIC of PTZ) on the morphology and physiology of E. coli. For this purpose, the bacteria used in the tests were grown for determined time in medium with 0.5 x MIC of PTZ (filamentous cells) and also in medium without antibiotic. The cells that were treated with PTZ showed a greater MIC compared to the ones that were not treated; however, the minimum bactericidal concentration (MBC) found was lower. The growth of E. coli in medium containing antibiotic showed changes in bacterial morphology. The altered cells did not show differences in biochemical characteristics in relation to untreated ones, even when they were tested in the test medium containing 0.5 x MIC of PTZ. The presence of0.5 x MIC of PTZ changed the growth pattern of E. coli, decreasing its finalpopulation density, or delaying the beginning and/or the end of the exponential growth phase. Compared with cells grown in the absence of drugs, the bacteria in filamentous form expressed lower ability to form biofilm, motility and cell surface hydrophobicity, and increased sensitivity to oxidative stress. Finally, the expression profile of total proteins showed lower protein expression in treated cells. When normal and filamentous bacteria were tested in the presence of 0.5 x MIC of PTZ in some of these tests, the changes were even more significant. Challenging experimental animals with cells treated with 0.5 x CIM PTZ showed that they are apparently less aggressive than those not treated, which is consistent with the other data in this study.