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Derepressed beta‐lactamase production as a mediator of high‐level beta‐lactam resistance in pseudomonas cepacia
Author(s) -
Aronoff Stephen C.
Publication year - 1988
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.1950040203
Subject(s) - ceftazidime , piperacillin , microbiology and biotechnology , beta lactamase , isoelectric focusing , pseudomonas , pseudomonadaceae , mutant , strain (injury) , biology , isoelectric point , pseudomonadales , bacteria , escherichia coli , pseudomonas aeruginosa , biochemistry , enzyme , gene , genetics , anatomy
A mechanism of high‐level resistance to readily and poorly hydrolyzable betalactam substrates in Pseudomonas cepacia was identified using a hypersusceptible, betalactamase‐inducible, non‐CF clinical isolate, 75–26, and a drug‐resistant mutant derived from this strain. Inoculation of 75–26 onto agar containing 16 μg/ml of ceftazidime produced a stable, beta‐lactam‐resistant mutant at a frequency of 1.7 × 10 −5 . Baseline beta‐lactamase production by a representative mutant isolate (75–26z) was almost 40‐fold greater than the parent. Both strains produced major beta‐lactamase bands with isoelectric points of 6.9, 7.8, 8.1, 8.5, and 9.2 by isoelectric focusing. Compared with the parental strain, multiple satellite bands associated with the major beta‐lactamase bands were present in the mutant. Growth of an indicator strain, E. coli ATCC 25922, was inhibited by ceftazidime and piperacillin but was not inhibited after the compounds were preincubated with the beta‐lactamase preparation from 75–26z. Preincubation of ceftazidime with beta‐lactamase, followed by the addition of a beta‐lactamase inhibitor, inhibited the growth of the indicator strain; piperacillin failed to inhibit growth of the indicator strain in a similar experiment. One mechanism of high‐level resistance to both poorly and readily hydrolyzable beta‐lactam substrates in P. cepacia is derepressed chromosomal beta‐lactamase production. Pediatr Pulmonol 1988; 4:72–77.