Transport of tetracyclines into Escherichia coli requires a carboxamide group at the C2 position of the molecule.

Structural features of the tetracycline molecule required for transport into Escherichia coli were investigated by examining the uptake of various tetracycline analogues. Uptake was assessed by determining the ability of analogues to induce Tn10 encoded resistance to tetracycline and by direct transport assays using tetracycline susceptible bacteria. Seven tetracyclines (including tetracycline itself) were studied. Two of these compounds, chlorotetracyclinonitrile and tetracyclinonitrile were not accumulated by E. coli, which suggests that the carboxamide group at the C2 position of the tetracycline molecule is required for transport into bacteria.