Related Experiment Video
Updated: Sep 20, 2026

Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance
Published on: May 2, 2018
Comparative activity of meropenem against Pseudomonas aeruginosa strains with well-characterized resistance
1Department of Medical Microbiology, The London Hospital Medical College, UK.
Abstract:
Four major mechanisms cause resistance to beta-lactams in Pseudomonas aeruginosa: (i) cell wall impermeability gives broad-spectrum intrinsic resistance to all beta-lactams except imipenem, (i) loss of D-group outer membrane proteins correlates with narrow spectrum imipenem resistance, (iii) plasmid mediated beta-lactamases compromise antipseudomonal penicillins, cefoperazone and cefsulodin, and (iv) chromosomal beta-lactamase hyper-production compromises most beta-lactams except carbenicillin and imipenem. Meropenem was tested in vitro against P. aeruginosa isolates, mutants and transconjugants with these mechanisms. Meropenem had impaired activity (MIC 1-2 mg/l compared to 0.25 mg/l for sensitive isolates) for organisms with broad-spectrum intrinsic resistance. MICs of meropenem also were elevated (to 1-2 mg/l) for mutants with D2-protein-deficiency-associated imipenem resistance. Most plasmids encoding TEM, OXA or PSE beta-lactamases did not increase the MIC (0.12 mg/l) of meropenem for P. aeruginosa PU21. Decreased susceptibility (MIC 4 mg/l), however, was observed when plasmids coding the uncommon NPS-1, PSE-2 and OXA-3 enzymes were present in this strain. MICs of meropenem remained identical for chromosomal beta-lactamase-inducible P. aeruginosa strains and their enzyme-derepressed and basal mutants, indicating that the chromosomal beta-lactamase could not protect against the new carbapenem, regardless of its mode of expression.
Insights
Meropenem shows reduced effectiveness against Pseudomonas aeruginosa with intrinsic resistance or D2-protein deficiency. However, it maintains activity against strains with most common beta-lactamases, offering a potential treatment option.
Area of Science:
- Microbiology
- Antimicrobial Resistance
- Bacterial Pathogenesis
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen.
- Beta-lactam antibiotics are crucial for treating P. aeruginosa infections.
- Mechanisms of beta-lactam resistance in P. aeruginosa include cell wall impermeability, outer membrane protein loss, plasmid-mediated beta-lactamases, and chromosomal beta-lactamase hyper-production.
Purpose of the Study:
- To evaluate the in vitro activity of meropenem against Pseudomonas aeruginosa isolates expressing known resistance mechanisms.
- To determine if meropenem can overcome common resistance pathways in P. aeruginosa.
Main Methods:
- In vitro testing of meropenem against P. aeruginosa isolates, mutants, and transconjugants.
- Characterization of isolates based on four major beta-lactam resistance mechanisms.
- Determination of meropenem minimum inhibitory concentrations (MICs).
Main Results:
- Meropenem exhibited impaired activity against P. aeruginosa with broad-spectrum intrinsic resistance (MIC 1-2 mg/l) and D2-protein deficiency (MIC 1-2 mg/l).
- Most common plasmid-mediated beta-lactamases (TEM, OXA, PSE) did not significantly affect meropenem MICs (0.12 mg/l).
- Reduced susceptibility to meropenem (MIC 4 mg/l) was noted with specific uncommon beta-lactamases (NPS-1, PSE-2, OXA-3).
- Chromosomal beta-lactamase expression did not impact meropenem MICs.
Conclusions:
- Meropenem retains activity against P. aeruginosa strains possessing most common beta-lactam resistance mechanisms.
- Meropenem's efficacy may be compromised by intrinsic resistance and specific uncommon beta-lactamases.
- Meropenem demonstrates potential as a treatment option for P. aeruginosa infections, but resistance monitoring is essential.
Related Concept Videos
Antimicrobial Effectiveness
Gene Regulation in Microbial Communities: Quorum Sensing
Development of Antibiotic Resistance
Mechanism of Antibiotic Resistance in MRSA
Clinical Significance of Antibiotic Resistance

