Saccharin disrupts bacterial cell envelope stability and interferes with DNA replication dynamics
Saccharin has been part of the human diet for over 100 years, and there is a comprehensive body of evidence demonstrating that it can influence the gut microbiome, ultimately impacting human health. However, the precise mechanisms through which saccharin can impact bacteria have remained elusive. In this work, we demonstrate that saccharin inhibits cell division, leading to cell filamentation with altered DNA synthesis dynamics. We show that these effects on the cell are superseded by the formation of bulges emerging from the cell envelope, which ultimately trigger cell lysis. We demonstrate that saccharin can inhibit the growth of both Gram-negative and Gram-positive bacteria as well as disrupt key phenotypes linked to host colonisation, such as motility and biofilm formation. In addition, we test its potential to disrupt established biofilms (single-species as well as polymicrobial) and its capacity to re-sensitise multidrug-resistant pathogens to last-resort antibiotics. Finally, we present in vitro and ex vivo evidence of the versatility of saccharin as a potential antimicrobial by integrating it into an effective hydrogel wound dressing.
Authors
- Rubén de Dios (ORCID: https://orcid.org/0000-0001-6704-9149)
- Kavita Gadar (ORCID: https://orcid.org/0000-0002-7907-1076)
- Marius M. Haugland (ORCID: https://orcid.org/0000-0001-7017-344X)
- Ronan R. McCarthy (ORCID: https://orcid.org/0000-0002-7480-6352)
- Bhupender Singh (ORCID: https://orcid.org/0000-0001-5634-6252)
- Evgenia Maslova (ORCID: https://orcid.org/0009-0008-1885-3104)
- Christian S. Lentz (ORCID: https://orcid.org/0000-0001-7284-2264)
- Anna-Luisa Warnke (ORCID: https://orcid.org/0009-0006-0621-7878)
- Tom Killelea (ORCID: https://orcid.org/0000-0003-0974-8034)
- Edward L. Bolt (ORCID: https://orcid.org/0000-0002-5656-7706)
- Emma L Dunbar
- Chris R Proctor (ORCID: https://orcid.org/0000-0002-0036-7123)
- Jie Han (ORCID: https://orcid.org/0000-0002-7777-0455)
- Mohamed A. N. Soliman (ORCID: https://orcid.org/0000-0002-6392-6631)
- Christian Rudolph (ORCID: https://orcid.org/0000-0003-2493-3748)
- Stelinda Peros
- Dominika Krawiel
Institutions
- University of Wisconsin–Madison (US)
- University of Nottingham (GB)
- Queen's Medical Centre (GB)
- Brunel University of London (GB)
- UiT The Arctic University of Norway (NO)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1038/s44321-025-00219-1
- Citations
- 5
- Primary Topic
- Bacterial biofilms and quorum sensing
- Type
- article
- Field-Weighted Citation Impact
- 4.03
Funders
- Wellcome Trust
- Tromsø Forskningsstiftelse
- British Heart Foundation
- Diabetes UK
- Academy of Medical Sciences
- National Centre for the Replacement Refinement and Reduction of Animals in Research
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council