Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity

Abstract Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence‐associated behaviours, suggesting food additives may be a niche for the discovery of novel anti‐virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame‐K (ace‐K), that have a major growth inhibitory effect on priority pathogens. We further characterise the impact of ace‐K on multidrug‐resistant Acinetobacter baumannii, demonstrating that it can disable virulence behaviours such as biofilm formation, motility and the ability to acquire exogenous antibiotic‐resistant genes. Further analysis revealed the mechanism of growth inhibition is through bulge‐mediated cell lysis and that cells can be rescued by cation supplementation. Antibiotic sensitivity assays demonstrated that at sub‐lethal concentrations, ace‐K can resensitise A. baumannii to last resort antibiotics, including carbapenems. Using a novel ex vivo porcine skin wound model, we show that ace‐K antimicrobial activity is maintained in the wound microenvironment. Our findings demonstrate the influence of artificial sweeteners on pathogen behaviour and uncover their therapeutic potential.