Non-antibiotic pharmaceuticals are toxic against *Escherichia coli* with no evolution of cross-resistance to antibiotics

Antimicrobial resistance is a global concern, exacerbated by pharmaceutical plant effluent. This study investigated the toxicity of four non-antibiotic pharmaceuticals (acetaminophen, ibuprofen, propranolol, metformin) and titanium dioxide against *E. coli*, and whether long-term exposure selects for cross-resistance to antibiotics. All compounds reduced *E. coli* growth, with ibuprofen causing upregulation of stress response and multidrug efflux genes. However, 30-day exposure did not select for significant genetic changes or cross-resistance to antibiotics, suggesting these compounds, at environmentally relevant concentrations, do not select for antibiotic cross-resistance in *E. coli*.

Rebecca J. Hall, Ann E. Snaith, Sarah J. Element, Robert A. Moran, Hannah Smith, Elizabeth A. Cummins, Michael J. Bottery, Kaniz F. Chowdhury, Dipti Sareen, Iqbal Ahmad, Jessica M. A. Blair, Laura J. Carter, Alan McNally