Carbapenem Resistance Mechanisms in Pseudomonas Aeruginosa

The emergence of carbapenem resistance in Pseudomonas aeruginosa poses a significant challenge to global health, owing to the bacterium’s intrinsic adaptability and the clinical importance of carbapenems as last-line agents. Resistance arises through a combination of intrinsic mechanisms—such as reduced permeability via loss or mutation of the outer membrane porin OprD, overproduction of the chromosomal AmpC β-lactamase and activation of multidrug efflux systems (notably the MexAB-OprM and MexXY-OprM pumps)—and acquired mechanisms involving horizontal transfer of carbapenemase genes. Metallo-β-lactamases (IMP, VIM, NDM) and serine carbapenemases (OXA variants) are commonly carried on mobile elements such as integrons, transposons and plasmids, facilitating rapid dissemination across clinical settings. In addition, biofilm formation, outer membrane modifications and co-occurrence of resistance-enhancing mutations further reduce susceptibility. These mechanisms often act in concert, amplifying resistance levels and complicating therapeutic intervention. Surveillance of high-risk clones and genotypic markers is essential for infection control, while advances in in silico and phenotypic diagnostics are refining the prediction of resistance phenotypes. Effective mitigation relies on antimicrobial stewardship, novel inhibitor development and precise combination regimens designed to suppress resistance emergence.

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Carbapenem Resistance Mechanisms in Pseudomonas Aeruginosa publication trend

The graph below shows the total number of articles in carbapenem resistance mechanisms in pseudomonas aeruginosa across all publications each year (not limited to Nature Index journals).

Technical terms

OprD: An outer membrane porin specific for basic amino acids and carbapenems; loss or mutation reduces drug uptake.

AmpC β-lactamase: A chromosomally encoded enzyme that hydrolyses cephalosporins and, when overproduced, contributes to carbapenem resistance.

Efflux pump (Mex system): A membrane-bound transport protein complex (e.g. MexAB-OprM) that expels antibiotics from the cell, decreasing intracellular drug concentration.

Metallo-β-lactamase: A class B carbapenemase requiring zinc ions to hydrolyse β-lactams, often carried on mobile genetic elements.

Integron: A genetic platform that captures and expresses resistance gene cassettes, facilitating the accumulation and transfer of antibiotic-resistance determinants.

References

1. Molecular pharmacodynamics of meropenem for nosocomial pneumonia caused by Pseudomonas aeruginosa. mBio (2024).
2. PorinPredict: In Silico Identification of OprD Loss from WGS Data for Improved Genotype-Phenotype Predictions of P. aeruginosa Carbapenem Resistance. Microbiology Spectrum (2023).
3. Genomic Characterization of IMP-Producing Pseudomonas aeruginosa in Bulgaria Reveals the Emergence of IMP-100, a Novel Plasmid-Mediated Variant Coexisting with a Chromosomal VIM-4 †. Microorganisms (2023).