Dataset Information

Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

ABSTRACT: Klebsiella oxytoca mutants resistant to a variety of beta-lactams were obtained in vitro on aztreonam. Constitutive beta-lactamase production was much higher in the mutants than in the susceptible strains (75-fold). The only difference observed in these mutants compared with the susceptible strains were point mutations in the Pribnow box: a transversion (G-->T) in the first base for one mutant or a transition (G-->A) in the fifth base of the -10 consensus sequence for the other three mutants. The transcriptional output of the beta-lactamase gene (blaOXY) from the mutants was significantly higher than that of the blaOXY gene from the susceptible strains.

SUBMITTER: Fournier B

PROVIDER: S-EPMC162743 | biostudies-other | 1995 Jun

REPOSITORIES: biostudies-other

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Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

Fournier B B Lu C Y CY Lagrange P H PH Krishnamoorthy R R Philippon A A

Antimicrobial agents and chemotherapy 19950601 6

Klebsiella oxytoca mutants resistant to a variety of beta-lactams were obtained in vitro on aztreonam. Constitutive beta-lactamase production was much higher in the mutants than in the susceptible strains (75-fold). The only difference observed in these mutants compared with the susceptible strains were point mutations in the Pribnow box: a transversion (G-->T) in the first base for one mutant or a transition (G-->A) in the fifth base of the -10 consensus sequence for the other three mutants. Th ...[more]

PMID: 7574532

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Project description:Klebsiella oxytoca complex (KoC) species may overproduce their chromosomal class A OXY β-lactamases, conferring reduced susceptibility to piperacillin-tazobactam, expanded-spectrum cephalosporins and aztreonam. Moreover, since clavulanate maintains its ability to inhibit these enzymes, the resulting resistance phenotype may falsely resemble the production of acquired extended-spectrum β-lactamases (ESBLs). In this work, a collection of 44 KoC strains of human and animal origin was characterized with whole-genome sequencing (WGS) and broth microdilution (BMD) susceptibility testing. Comparison of ESBL producers (n = 11; including CTX-M-15 [n = 6] and CTX-M-1 [n = 5] producers) and hyperproducers of OXYs (n = 21) showed certain phenotypic differences: piperacillin-tazobactam (MIC90s: 16 versus >64 μg/mL), cefotaxime (MIC90s: 64 versus 4 μg/mL), ceftazidime (MIC90s: 32 versus 4 μg/mL), cefepime (MIC90s: 8 versus 4 μg/mL) and associated resistance to non-β-lactams (e.g., trimethoprim-sulfamethoxazole: 90.9% versus 14.3%, respectively). However, a clear phenotype-based distinction between the two groups was difficult. Therefore, we evaluated 10 different inhibitor-based confirmatory tests to allow such categorization. All tests showed a sensitivity of 100%. However, only combination disk tests (CDTs) with cefepime/cefepime-clavulanate and ceftazidime/ceftazidime-clavulanate or the double-disk synergy test (DDST) showed high specificity (100%, 95.5%, and 100%, respectively). All confirmatory tests in BMD or using the MIC gradient strip did not perform well (specificity, ≤87.5%). Of note, ceftazidime/ceftazidime-avibactam tests also exhibited low specificity (CDT, 87.5%; MIC gradient strip, 77.8%). Our results indicate that standard antimicrobial susceptibility profiles can raise some suspicion, but only the use of cefepime/cefepime-clavulanate CDT or DDST can guarantee distinction between ESBL-producing KoC strains and those hyperproducing OXY enzymes.

Dataset Information

Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

Publications

Point mutation in the pribnow box, the molecular basis of beta-lactamase overproduction in Klebsiella oxytoca.

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