FREQUENCY AND MECHANISM OF RESISTANCE TO ANTIBACTERIAL ACTION OF ZM-240401, (6S)-6-FLUORO-SHIKIMIC ACID

Spontaneous resistance to (6S)-6-fluoro-shikimic acid arose in Escheri chia coil and other enterobacteria at high frequencies, between 10(-5) and 10(-4). Two resistant variants of E. coil were tested for their s usceptibilities to the diastereomeric compound, (6R)-6-fluoro-shikimat e, and both of them had become resistant to this compound as well. (6S )-6-Fluoro-shikimate-resistant variants of E. coli generally failed to transport [C-14] shikimate. In E. coil K-12, (6S)-6-fluoro-shikimate resistance cotransduced with his at the same frequency as shiA, a gene locus that governs shikimate transport phenotypes. We propose that th e loss of susceptibility to (6S)6-fluoro-shikimic acid in spontaneous resistant variants is due to the loss of activity of the transport sys tem by which it enters the bacterial cytoplasm.