PMID:15155219
| Citation |
Hirata, T, Saito, A, Nishino, K, Tamura, N and Yamaguchi, A (2004) Effects of efflux transporter genes on susceptibility of Escherichia coli to tigecycline (GAR-936). Antimicrob. Agents Chemother. 48:2179-84 |
|---|---|
| Abstract |
The activity of tigecycline, 9-(t-butylglycylamido)-minocycline, against Escherichia coli KAM3 (acrB) strains harboring plasmids encoding various tetracycline-specific efflux transporter genes, tet(B), tet(C), and tet(K), and multidrug transporter genes, acrAB, acrEF, and bcr, was examined. Tigecycline showed potent activity against all three Tet-expressing, tetracycline-resistant strains, with the MICs for the strains being equal to that for the host strain. In the Tet(B)-containing vesicle study, tigecycline did not significantly inhibit tetracycline efflux-coupled proton translocation and at 10 microM did not cause proton translocation. This suggests that tigecycline is not recognized by the Tet efflux transporter at a low concentration; therefore, it exhibits significant antibacterial activity. These properties can explain its potent activity against bacteria with a Tet efflux resistance determinant. Tigecycline induced the Tet(B) protein approximately four times more efficiently than tetracycline, as determined by Western blotting, indicating that it is at least recognized by a TetR repressor. The MICs for multidrug efflux proteins AcrAB and AcrEF were increased fourfold. Tigecycline inhibited active ethidium bromide efflux from intact E. coli cells overproducing AcrAB. Therefore, tigecycline is a possible substrate of AcrAB and its close homolog, AcrEF, which are resistance-modulation-division-type multicomponent efflux transporters. |
| Links |
PubMed PMC415592 Online version:10.1128/AAC.48.6.2179-2184.2004 |
| Keywords |
Blotting, Western; Cell Membrane/drug effects; Cell Membrane/metabolism; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/metabolism; Ethidium/metabolism; Microbial Sensitivity Tests; Minocycline/analogs & derivatives; Minocycline/pharmacology; Multidrug Resistance-Associated Proteins/genetics; Multidrug Resistance-Associated Proteins/metabolism; Plasmids/genetics; Protons; Quinacrine/diagnostic use; Tetracycline Resistance/genetics; Tetracyclines/pharmacology |
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