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Genetics of extended-spectrum beta-lactamases
1Lahey Clinic, Burlington, Massachusetts 01805.
Summary
Bacteria are evolving resistance to advanced antibiotics like oxyimino-beta-lactams by modifying enzymes and acquiring new resistance genes. This adaptation poses a significant challenge to treating bacterial infections effectively.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Resistance
Background:
- Bacteria have developed resistance to oxyimino-beta-lactams, a class of antibiotics.
- This resistance is mediated by alterations in plasmid-mediated beta-lactamases.
Purpose of the Study:
- To investigate the mechanisms by which bacteria adapt to oxyimino-beta-lactams.
- To understand the evolution of extended-spectrum beta-lactamases (ESBLs) and gene capture conferring resistance.
Main Methods:
- Analysis of amino acid substitutions in TEM and SHV beta-lactamase families.
- Identification of compensatory up-promoter events.
- Tracking the transfer of chromosomal resistance genes via plasmids.
Main Results:
- Increased amino acid substitutions in TEM and SHV ESBLs enhance activity against oxyimino-substrates, but reduce intrinsic efficiency.
- Compensatory up-promoter events lead to increased enzyme expression.
- Plasmid-mediated capture of chromosomal genes from Enterobacter cloacae, Citrobacter freundii, and Pseudomonas aeruginosa confers resistance to both alpha-methoxy- and oxyimino-beta-lactams in Klebsiella pneumoniae and Escherichia coli.
Conclusions:
- Bacterial adaptation to oxyimino-beta-lactams involves both enzyme modification and horizontal gene transfer.
- These mechanisms contribute to the growing challenge of antibiotic resistance, impacting treatment efficacy.