1887

Abstract

Multidrug resistance (MDR) genes are abundant in genomes, and yet these bacteria are generally drug sensitive under routine laboratory conditions, indicating low or no expression of these genes. Drug-resistant mutations have been isolated that lie in regulatory genes adjacent to the MDR genes, suggesting that resistance arises by derepression. This study identified a divergently oriented pair consisting of a TetR-family regulator () and a major facilitator-family MDR pump () gene in , which is widely conserved in species. EbrS represses transcription of as well as its own transcription. Deletion of causes overexpression of , resulting in elevated resistance to many drugs. The and promoters were used in a reporter system to test inducibility by various chemicals. Among the 15 compounds (including five EbrC target drugs) tested, none induced transcription. On the other hand, the promoter was induced by rifampicin and high concentrations of calcium and magnesium. Deletion of did not change rifampicin sensitivity, indicating that the EbrC pump is not involved in rifampicin efflux. Moreover, deletion of caused retardation of colony growth on selected media, and the defect could be suppressed by supplementation with high concentrations of Ca, Mg, Na or K. Based on these results, it is proposed that the primary biological role of most MDR systems in species is not removal of extrinsic drugs, but rather export of specific toxic compounds endogenously synthesized during growth.

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2007-04-01
2020-08-12
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