Interplay between drug efflux and antioxidants in Escherichia coli resistance to antibiotics.
We investigated possible cross talk between endogenous antioxidants glutathione, spermidine, and glutathionylspermidine and drug efflux in Escherichia coli. We found that cells lacking either spermidine or glutathione are less susceptible than the wild type to novobiocin and certain aminoglycosides. In contrast, exogenous glutathione protects against both bactericidal and bacteriostatic antibiotics. The glutathione protection does not require the AcrAB efflux pump but fails in cells lacking TolC because exogenous glutathione is toxic to these cells.
Dhamdhere
Girija
G
Department of Chemistry and Biochemistry, University of Oklahoma, 620 Parrington Oval, Room 208, Norman, OK 73019, USA.
Krishnamoorthy
Ganesh
G
Zgurskaya
Helen I
HI
D000617:Aminoglycosides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism*; D004917:Erythromycin / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism; D007612:Kanamycin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009675:Novobiocin / Q000494:pharmacology; D013095:Spermidine / Q000031:analogs & derivatives / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000975:Antioxidants; D009675:Novobiocin; C012333:glutathionylspermidine; D007612:Kanamycin; D004917:Erythromycin; D005978:Glutathione; D013095:Spermidine