pH effects on the inhibition of extended-spectrum and classical TEM beta-lactamases by penicillanic acid sulphones.
MICs of piperacillin with tazobactam or sulbactam (4 mg/L) were higher at pH 6.5 than at pH 8.0 for Escherichia coli transconjugants with TEM-1 or TEM-2 enzymes, but not for those with TEM-3 or TEM-10 enzymes. Investigation showed: (i) all four enzymes were less sensitive to sulphones at pH 6.5 than at pH 8.0; (ii) pH effects on MICs arose also for the TEM-3 and TEM-10 producers at lower sulphone concentrations; (iii) the TEM-3 and TEM-10 producers formed less enzyme than those with TEM-1 and TEM-2 and (iv) pH effects on the MICs for TEM-1 producers depended on enzyme quantity. We conclude that all four TEM enzymes have pH-dependent susceptibility to sulphones, but whether this affects MICs depends on the inhibitor:enzyme ratio achieved in the bacteria.
Fornara
A M
AM
Royal London School of Medicine and Dentistry, UK.
Danel
F
F
Livermore
D M
DM
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003227:Conjugation, Genetic; D003470:Culture Media; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000494:pharmacology*; D010406:Penicillins / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D003470:Culture Media; D010406:Penicillins; D013450:Sulfones; D065093:beta-Lactamase Inhibitors; D010397:Penicillanic Acid; D001618:beta-Lactamases