title: Frequency and mechanism of resistance to antibacterial action of ZM 240401, (6S)-6-fluoro-shikimic acid.
abstract: Spontaneous resistance to (6S)-6-fluoro-shikimic acid arose in Escherichia coli and other enterobacteria at high frequencies, between 10(-5) and 10(-4). Two resistant variants of E. coli were tested for their susceptibilities to the diastereomeric compound, (6R)-6-fluoro-shikimate, 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 [14C]shikimate. In E. coli 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 the loss of susceptibility to (6S)-6-fluoro-shikimic acid in spontaneous resistant variants is due to the loss of activity of the transport system by which it enters the bacterial cytoplasm.
authors.affiliation: ZENECA Pharmaceuticals, Alderley Park, Macclesfield, United Kingdom.
authors.forename: C D
authors.initials: CD
authors.lastname: Ewart
authors.forename: D A
authors.initials: DA
authors.lastname: Jude
authors.forename: J L
authors.initials: JL
authors.lastname: Thain
authors.forename: W W
authors.initials: WW
authors.lastname: Nichols
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004754:Enterobacter / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D012765:Shikimic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: C087313:6-fluoroshikimic acid; D000900:Anti-Bacterial Agents; D012765:Shikimic Acid