The Effect of Antibiotic and Nonantibiotic Drugs on Plasmid-Mediated Bacterial Conjugation

The clinical utility of antibiotics has been eroded by the emergence of antibiotic resistance. One major mechanism by which microorganisms develop resistance to antibiotics and nonantibiotics is by horizontal gene transfer (HGT) via plasmid-mediated conjugation.

To investigate the impact of specific antibiotics and nonantibiotics on plasmid-mediated bacterial conjugation and elimination.

The minimum inhibitory concentration (MIC) of the selected antibiotics and nonantibiotics was determined for Escherichia coli (ATCC 25922) using the broth microdilution method. The anticonjugant activities of the test drugs were assessed using the liquid conjugation assay on plasmids IncN plasmid pKM101, IncP plasmid pUB307, and IncW plasmid R7K in E. coli. Additionally, the ability of the test drugs to eliminate and/or cure plasmids was determined.

At subinhibitory concentrations, several antibiotics-including azithromycin, doxycycline, and ceftriaxone-and nonantibiotic pharmaceuticals, such as amlodipine and propranolol, facilitated the horizontal transfer of plasmid-borne antibiotic-resistant genes in a plasmid-specific manner. Amlodipine notably enhanced the conjugative transfer of IncN plasmid pKM101 by 2.52-fold and the IncP plasmid pUB307 by 4.23-fold. Propranolol also increased the transfer of IncN plasmid pKM101, albeit modestly (1.14-fold). Plasmid curing activity was broad and nonselective in the case of amlodipine, doxycycline, glibenclamide, and levofloxacin, whereas propranolol exhibited plasmid-specificity curing activity, particularly against IncW plasmid R7K.

These findings demonstrate that antibiotics and nonantibiotic drugs can exert dual, context-dependent effects, simultaneously promoting plasmid transfer while eliminating specific plasmids. This plasmid-specific interplay highlights the complexity of drug-microbe interactions and underscores the need for careful evaluation of their roles in antimicrobial resistance dynamics.