The cryptic tetracycline resistance determinant on Tn4400 mediates tetracycline degradation as well as tetracycline efflux

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Abstract
Escherichia coli containing the cryptic tetracycline resistance determinant (class F) from the Bacteroides fragilis transposon Tn4400 on plasmid pGAT400 expressed a detoxification of tetracycline as well as an active efflux of tetracycline. This finding concurs with the report of detoxification for a related tetracycline resistance determinant from B. fragilis on Tn4351 (B. S. Speer and A. Salyers, J. Bacteriol. 170:1423-1429, 1987), which specifies a 10-fold-higher resistance than Tn4400. Inactivation of tetracycline occurred at an initial rate of congruent to 0.7 micrograms of tetracycline per h per 10(8) cells, as determined by biologic assay and chromatographic analysis. The detoxification is a chemical degradation which can occur in the absence of energy-dependent efflux. The products of this degradation were not substrates for active transport into susceptible cells or out of pGAT400-containing E. coli. These results indicate that Tn4400 mediates two functionally different mechanisms for tetracycline resistance: an active efflux of tetracycline and a degradation of tetracycline.