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