# Proteomic landscape of imipenem resistance in Pseudomonas aeruginosa: a comparative investigation between clinical and control strains

## TL;DR

This study compares the proteomic responses of a drug-resistant Pseudomonas aeruginosa strain and a control strain to understand how they resist imipenem.

## Contribution

The study reveals distinct proteomic strategies in a clinical strain versus a control strain for imipenem resistance.

## Key findings

- The clinical strain showed a stable proteomic profile, indicating pre-established resistance mechanisms.
- The control strain exhibited a reactive proteomic response, especially in stress and transport proteins.
- Uncharacterized proteins were upregulated in the clinical strain, suggesting novel resistance pathways.

## Abstract

The increasing prevalence of antimicrobial resistance (AMR) poses a significant challenge to global health, particularly with bacterial pathogens such as Pseudomonas aeruginosa, a notorious cause of nosocomial infections. This study focuses on the comparative proteomic analysis of an imipenem-resistant strain of P. aeruginosa, a representative of world epidemic clone ST235, and a wildtype control strain, P. aeruginosa ATCC 27853, in response to varying concentrations of imipenem. Using label-free quantification (LFQ) and gene ontology (GO) enrichment analyses, we identified significant differences in the proteomic responses between the two strains. The clinical strain exhibited a stable proteomic profile across the imipenem gradient, suggesting pre-established and efficient resistance mechanisms that do not require extensive reconfiguration under antibiotic pressure. In contrast, the control strain showed a broader, more reactive proteomic response, particularly in proteins associated with membrane transport, stress response, and biofilm formation. Notably, uncharacterized proteins were significantly upregulated in the clinical strain, indicating potential novel resistance mechanisms. These findings highlight the distinct strategies employed by the two strains, with the clinical strain’s stable resistance mechanisms contrasting sharply with the control strain’s reactive approach. The study underscores the importance of further research into the uncharacterized proteins that may play crucial roles in antibiotic resistance, potentially leading to new therapeutic targets in the fight against AMR.