Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2023

Currently, at least 1.27 million annual deaths are caused by antimicrobial resistance globally [1]. Although non-antibiotic pharmaceuticals account for 95% of the drug market share, little is known about the association between non-antibiotic pharmaceuticals and the dissemination of antibiotic resistance. By establishing multiple bacterial antibiotic resistance development models (including mutation, conjugation and transformation) to investigate antibiotic-like effects of common non-antibiotic drugs (e.g. antidepressants and anti-inflammatories), we found that these non-antibiotic pharmaceuticals not only induce the emergence of antibiotic resistance through mutation but also promote the spread of antibiotic resistance via conjugation and transformation (Figure 1) [2-5].

Figure 1. Pathways of non-antibiotic pharmaceuticals to spread antibiotic resistance and the scope of this abstract.

In general, various non-antibiotic pharmaceuticals were found to facilitate the emergence and spread of antibiotic resistance. For the mutation experiment, antidepressant fluoxetine was found to increase the mutation rate of E. coli up to 5.0 × 10⁷ fold in a dose-time pattern. Isolated mutants also exhibited resistance against multiple antibiotics that is over 8 times higher than the non-treated controls [2].

For the conjugation experiment, the antiepileptic drug carbamazepine, various antidepressants (duloxetine, sertraline, fluoxetine and bupropion), anti-inflammatories, ibuprofen, naproxen, diclofenac, lipid-lowering drug gemfibrozil, and the β-blocker propranolol were found to increase the conjugative transfer of ARGs in pure culture bacterial models [3].

For the transformation model, various antidepressants (duloxetine, sertraline, fluoxetine and bupropion) could promote the transformation of ARGs [4].

We further upgraded the pure culture models to the actual environmental microbiome model, and found that non-antibiotic pharmaceuticals at environmentally relevant concentrations can promote the conjugative transfer of antibiotic resistance across entire wastewater activated sludge microbial communities. More importantly, genetic profiling by 16S rRNA sequencing on sorted transconjugants revealed the acquisition of ARGs by opportunistic human pathogens (such as Acinetobacter and Legionella spp.) was promoted under pharmaceuticals exposure [5].

Our findings provide the first insight into non-antibiotic pharmaceuticals-facilitated acquisition of antibiotic resistance by various microorganisms (including opportunistic pathogens) via mutation, conjugation and transformation. Our study warns of the contribution of non-antibiotic pharmaceuticals to the dissemination of antibiotic resistance in the environment at the community level.