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 i...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-01-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216397 |
| _version_ | 1797280700893757440 |
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| author | Rubén de Dios Chris R Proctor Evgenia Maslova Sindija Dzalbe Christian J Rudolph Ronan R McCarthy |
| author_facet | Rubén de Dios Chris R Proctor Evgenia Maslova Sindija Dzalbe Christian J Rudolph Ronan R McCarthy |
| author_sort | Rubén de Dios |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:44:57Z |
| format | Article |
| id | doaj.art-1f873535607c445a86cfeef0d7b1bd89 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:44:57Z |
| publishDate | 2023-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-1f873535607c445a86cfeef0d7b1bd892024-03-03T06:36:52ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-01-01151n/an/a10.15252/emmm.202216397Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activityRubén de Dios0Chris R Proctor1Evgenia Maslova2Sindija Dzalbe3Christian J Rudolph4Ronan R McCarthy5Division of Biosciences, Department of Life Sciences, Centre of Inflammation Research and Translational Medicine, College of Health, Medicine and Life Sciences Brunel University London Uxbridge UKDivision of Biosciences, Department of Life Sciences, Centre of Inflammation Research and Translational Medicine, College of Health, Medicine and Life Sciences Brunel University London Uxbridge UKDivision of Biosciences, Department of Life Sciences, Centre of Inflammation Research and Translational Medicine, College of Health, Medicine and Life Sciences Brunel University London Uxbridge UKDivision of Biosciences, Department of Life Sciences, Centre of Inflammation Research and Translational Medicine, College of Health, Medicine and Life Sciences Brunel University London Uxbridge UKDivision of Biosciences, Department of Life Sciences, Centre for Genome Engineering and Maintenance, College of Health, Medicine and Life Sciences Brunel University London Uxbridge UKDivision of Biosciences, Department of Life Sciences, Centre of Inflammation Research and Translational Medicine, College of Health, Medicine and Life Sciences Brunel University London Uxbridge UKAbstract 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.https://doi.org/10.15252/emmm.202216397Acinetobacter baumanniiantimicrobialartificial sweetenerbiofilmcarbapenem |
| spellingShingle | Rubén de Dios Chris R Proctor Evgenia Maslova Sindija Dzalbe Christian J Rudolph Ronan R McCarthy Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity EMBO Molecular Medicine Acinetobacter baumannii antimicrobial artificial sweetener biofilm carbapenem |
| title | Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity |
| title_full | Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity |
| title_fullStr | Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity |
| title_full_unstemmed | Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity |
| title_short | Artificial sweeteners inhibit multidrug‐resistant pathogen growth and potentiate antibiotic activity |
| title_sort | artificial sweeteners inhibit multidrug resistant pathogen growth and potentiate antibiotic activity |
| topic | Acinetobacter baumannii antimicrobial artificial sweetener biofilm carbapenem |
| url | https://doi.org/10.15252/emmm.202216397 |
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