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beta-Lactamase of Pseudomonas pseudomallei and its contribution to antibiotic resistance
D M Livermore1, P Y Chau, A I Wong
1Department of Microbiology, University of Hong Kong.
Abstract:
beta-Lactamase production was examined in nine strains of Pseudomonas pseudomallei isolated from human, animal and environmental sources in Thailand and Hong Kong. All produced the same weakly inducible, membrane associated chromosomal cephalosporinase, which had a molecular weight of 29,500 and an isoelectric point of 7.4-7.7. The enzyme resembled the cefuroximases of Ps. cepacia and Proteus vulgaris, but differed from the Class I cephalosporinases typical of Ps. aeruginosa and most enterobacteria, in being strongly active against carbenicillin, cefotaxime and cefuroxime and in being inactivated readily by clavulanic acid. Synergy experiments with clavulanic acid investigated the enzyme's contribution to antibiotic resistance, and these results broadly correlated with those of in-vitro hydrolysis assays. Thus, ampicillin, carbenicillin, cefoperazone, cefotaxime, cefuroxime and cephalothin, which were hydrolysed in vitro, were potentiated four to 64-fold by 2 mg/l clavulanic acid; but cefoxitin, ceftazidime, cloxacillin and imipenem, which appeared stable in vitro, were potentiated four-fold or less.
Insights
Nine Pseudomonas pseudomallei strains produce a cephalosporinase enzyme. This enzyme contributes to antibiotic resistance, showing activity against several beta-lactam antibiotics and inactivation by clavulanic acid.
Area of Science:
- Microbiology
- Biochemistry
- Pharmacology
Background:
- Pseudomonas pseudomallei is an opportunistic pathogen.
- Beta-lactamase enzymes are a major mechanism of antibiotic resistance.
- Understanding beta-lactamase activity in P. pseudomallei is crucial for effective treatment.
Purpose of the Study:
- To characterize the beta-lactamase produced by Pseudomonas pseudomallei strains.
- To investigate the enzyme's activity against various beta-lactam antibiotics.
- To assess the role of clavulanic acid in overcoming antibiotic resistance mediated by this enzyme.
Main Methods:
- Isolation and characterization of nine P. pseudomallei strains from diverse sources.
- Determination of enzyme molecular weight and isoelectric point.
- In vitro hydrolysis assays and synergy experiments with clavulanic acid.
Main Results:
- All nine strains produced a single, weakly inducible, membrane-associated cephalosporinase.
- The enzyme exhibited activity against carbenicillin, cefotaxime, and cefuroxime.
- Clavulanic acid readily inactivated the enzyme and potentiated the activity of several beta-lactam antibiotics against P. pseudomallei.
Conclusions:
- The characterized cephalosporinase contributes to beta-lactam antibiotic resistance in P. pseudomallei.
- The enzyme's susceptibility to clavulanic acid suggests potential therapeutic strategies.
- Further research into beta-lactamase inhibitors is warranted for treating P. pseudomallei infections.