Human-targeted drugs impact antibiotic sensitivity and growth of Campylobacter jejuni

Authors

Zannoni, A., Olayo-Alarcon, R., Amstalden, M. K., Feldl, M., Wuerz, R., Bruchhardt, T., Kullmann, J., Svensson, S. L., Sotriffer, C., Alzheimer, M., Mueller, C. L., Brochado, A. R., Sharma, C. M.

Abstract

Antibiotic resistance is increasingly recognized as a major threat to global health, yet the contribution of non-antibiotics to this problem remains poorly defined. Here, we established a transcriptional chemical genomics approach to map how 2,415 host-relevant small molecules influence stress-responsive promoters and fitness of the foodborne pathogen Campylobacter jejuni. This screen uncovered widespread activation of the CmeABC efflux pump by diverse compounds, including several human-targeted drugs. Notably, ibuprofen, one of the most widely used non-steroidal anti-inflammatory drugs worldwide, induced efflux pump expression and thereby enhanced bacterial tolerance to ciprofloxacin. We also identified multiple commensal-sparing human-targeted drugs with growth-inhibitory activity against C. jejuni, highlighting opportunities for pathogen-targeted drug repurposing. Together, our findings reveal that non-antibiotic drugs can both promote resistance-associated phenotypes and selectively suppress pathogen growth. This underscores the need to consider collateral drug effects on bacterial physiology when designing strategies to curb the burden of antimicrobial resistance.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 07 Oct 2026.

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