MUTATIONS IN THE TETA(B) GENE THAT CAUSE A CHANGE IN SUBSTRATE-SPECIFICITY OF THE TETRACYCLINE EFFLUX PUMP

The tetA(B) gene from transposon Tn10 fails to mediate resistance to the novel tetracycline analog 9-(dimethylglycylamido)minocycline (DMG-Mino) (P. E. Sum, V. J. Lee, R. T. Testa, J. J. Hlavka, G. A. Ellestad, J. D. Bloom, Y. Gluzman, and F. P. Tally, J. Med. Chem. 37:184-188,1994; R. T. Testa, P. Petersen, N. V. Jacobus, P. E. Sum, V. J. Lee, and F. P. Tally, Antimicrob. Agents Chemother. 37:2270-2277, 1993). Mutations in either of two codons of tetA(B) that resulted in increased resistance to DMG-Mino also caused diminished resistance to tetracycline, identifying amino acid residues critical for the recognition of tetracycline.