Ibuprofen prevents the conjugative transfer of plasmid-mediated antimicrobial resistance genes

Area of Science:

• Microbiology
• Molecular Biology
• Pharmacology

Background:

• Multidrug-resistant (MDR) bacteria present a critical global health challenge.
• The spread of antibiotic resistance genes, particularly via plasmid conjugation, exacerbates this threat.

Purpose of the Study:

• To investigate the potential of ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), to inhibit bacterial conjugation.
• To explore the underlying mechanisms by which ibuprofen affects conjugation and antibiotic resistance gene transfer.

Main Methods:

• Tested ibuprofen's effect on the conjugation of the RP4 plasmid and clinical plasmids carrying various resistance genes (mcr-1, blaNDM, blaKPC, tet(X4), tmexCD1-toprJ1).
• Conducted mechanistic studies to elucidate how ibuprofen impacts bacterial processes related to conjugation.

Main Results:

• Ibuprofen demonstrated significant inhibition of plasmid conjugation across multiple resistance gene types.
• Mechanistic investigations revealed that ibuprofen reduces bacterial ATP production and downregulates key conjugation-related genes.

Conclusions:

• Ibuprofen exhibits potent anti-conjugation activity, offering a novel strategy to curb the dissemination of multidrug resistance.
• These findings suggest ibuprofen could be a valuable adjunct therapy in managing infections caused by MDR bacteria.