Jacobs J Y, Livermore D M, Davy K W
J Antimicrob Chemother. 1984 Sep;14(3):221-9. doi: 10.1093/jac/14.3.221.
Azlocillin, mezlocillin and piperacillin are weak substrates for the chromosomal beta-lactamase of Pseudomonas aeruginosa, and hydrolysis kinetics were calculated. Enzyme function in the living cell was studied by comparing antibiotic activity against a typical Ps. aeruginosa strain with inducible beta-lactamase expression with antibiotic activity against beta-lactamase uninducible and constitutive mutants. The inducible organism was less sensitive than its uninducible mutant to all three agents; this difference was more apparent at high inocula than low and in broth than in agar. These differences involved both enzyme induction and selection of genotypically enzyme derepressed variants. The penicillins were not, however, efficient beta-lactamase inducers at low concentrations and their activity against the inducible organism was antagonized by more potent inducers. Secondary inducers did not antagonize antibiotic activity against beta-lactamase uninducible and constitutive organisms. The beta-lactamase constitutive mutants were highly resistant to the three antibiotics tested.
阿洛西林、美洛西林和哌拉西林是铜绿假单胞菌染色体β-内酰胺酶的弱底物，并计算了水解动力学。通过比较针对具有诱导型β-内酰胺酶表达的典型铜绿假单胞菌菌株的抗生素活性与针对β-内酰胺酶非诱导型和组成型突变体的抗生素活性，研究了活细胞中的酶功能。诱导型菌株对所有三种药物的敏感性低于其非诱导型突变体；这种差异在高接种量时比低接种量时更明显，在肉汤中比在琼脂中更明显。这些差异既涉及酶诱导，也涉及基因型酶去阻遏变体的选择。然而，青霉素在低浓度时不是有效的β-内酰胺酶诱导剂，更有效的诱导剂会拮抗它们对诱导型菌株的活性。二级诱导剂不会拮抗针对β-内酰胺酶非诱导型和组成型菌株的抗生素活性。β-内酰胺酶组成型突变体对所测试的三种抗生素高度耐药。
