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

• Published in: EMBO molecular medicine 2023-01, Vol.15 (1), p.e16397-n/a
• Main Authors: de Dios, Rubén, Proctor, Chris R, Maslova, Evgenia, Dzalbe, Sindija, Rudolph, Christian J, McCarthy, Ronan R
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotic resistance; Antibiotics; antimicrobial; Antimicrobial activity; Antimicrobial agents; Antimicrobial resistance; artificial sweetener; Artificial sweeteners; Bacteria; biofilm; Biofilms; carbapenem; Carbapenems; Carbapenems - pharmacology; Carbapenems - therapeutic use; Cyclamates; Drug resistance; Drug Resistance, Multiple, Bacterial; Food additives; Humans; Investigations; Lysis; Microenvironments; Multidrug resistance; Multidrug resistant organisms; Pathogens; Phytochemicals; Saccharin; Sodium; Sweeteners; Sweetening Agents - pharmacology; Swine; Virulence; Wounds
• ISSN: 1757-4676; 1757-4684; 1757-4684
• DOI: 10.15252/emmm.202216397

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. Synopsis Artificial sweeteners can inhibit the growth of multidrug‐resistant pathogens, disrupt virulence associated behaviours and potentiate antibiotic activity. In wound models the sweetener, Acesulfame K, shows potential as a topical wound treatment. Artificial sweeteners can significantly impact the growth of bacterial pathogens. Ace‐K can inhibit a range of virulence traits such as biofilm formation, motility and natural transformation. It weakens the bacterial cell membrane leading to loss of morphology and bulge‐mediated cell lysis. It can also potentiate the activity of antibiotics including carbapenems. Ace‐K shows clinical potential as a topical wound therapeutic. Artificial sweeteners can inhibit the growth of multidrug resistant pathogens, disrupt virulence associated behaviours and potentiate antibiotic activity. In wound models the sweetener, Acesulfame K, shows potential as a topical wound treatment.