RESUMO
Efflux mechanisms protect bacterial cells by pumping out toxic compounds and actively contribute to bacterial multidrug resistance. Agents inhibiting efflux pumps are of interest for the control of multidrug-resistant bacterial infections. Herein we report the effects of new chloroquinoline derivatives that render resistant Enterobacter aerogenes isolates noticeably more susceptible to structurally unrelated antibiotics. In addition, some of these chloroquinolines increase the intracellular concentration of chloramphenicol. Some of the molecules tested in this work are able to inhibit the main efflux pump (AcrAB-TolC), which is involved in E. aerogenes antibiotic resistance.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Transporte/antagonistas & inibidores , Enterobacter aerogenes/efeitos dos fármacos , Quinolinas/farmacologia , Cloranfenicol/farmacocinética , Farmacorresistência Bacteriana , Enterobacter aerogenes/metabolismo , Testes de Sensibilidade MicrobianaRESUMO
Chloramphenicol has been reported to act as an inducer of the multidrug resistance in Escherichia coli. A resistant variant able to grow on plates containing 64 microg/ml chloramphenicol was obtained from the Enterobacter aerogenes ATCC 13048-type strain. Chloramphenicol resistance was due to an active efflux of this antibiotic and it was associated with resistance to fluoroquinolones and tetracycline, but not to aminoglycoside or beta-lactam antibiotics. MDR in the chloramphenicol-resistant variant is linked to the overexpression of the major AcrAB-TolC efflux system. This overexpression seems unrelated to the global Mar and the local AcrR regulatory pathways.
