Distinct proteomic profiles of clinical isolates show diversity of Pseudomonas aeruginosa colistin-resistance

Background Pseudomonas aeruginosa is a multidrug-resistant pathogenic bacterium that poses a substantial threat to global public health because of its resistance to antibiotics, and especially to last-resort colistin. The aim of this study is to perform a comparative analysis between the antibiotic-sensitive isolate A and the resistant isolate C (8 µg/mL for isolate A and 128 µg/mL for isolate C), with the intent of elucidating the discrete molecular mechanisms underpinning resistance. This investigation seeks to distinguish between pathways inherently expressed in the absence of antibiotic exposure (acquired resistance) and those activated in response to antibiotic challenge (induced resistance), thereby providing deeper insights into the multifaceted nature of antimicrobial resistance in P. aeruginosa. Results Proteomic analysis, performed under basal conditions and after exposure to increasing doses of colistin, revealed that, although both isolates have intrinsic resistance to several antimicrobials, the mechanisms underlying colistin resistance diverge significantly. While isolate A showed a stable proteomic response, characterized by the overexpression of proteins related to membrane remodeling and efflux systems, isolate C demonstrated a more dynamic response, evidenced by metabolic adaptations and oxidative stress mitigation mechanisms. These differences suggest that each isolate employs specific strategies to cope with antimicrobial pressure, which has direct implications for the choice of alternative therapies and the development of optimized dosing regimens. Conclusions The findings have direct implications for the choice of alternative therapies and the development of optimized dosing regimen. In summary, the results reinforce the complexity of resistance mechanisms in P. aeruginosa and highlight the importance of personalized therapeutic approaches for the management of infections caused by multidrug-resistant isolates. Supplementary Information The online version contains supplementary material available at 10.1186/s12014-026-09592-6.