Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds

Powell, Lydia C. ORCID: https://orcid.org/0000-0002-8641-0160, Cullen, Jason K., Boyle, Glen M., De Ridder, Tom, Yap, Pei-Yi, Xue, Wenya, Pierce, Carly J., Pritchard, Manon F., Menzies, Georgina E. ORCID: https://orcid.org/0000-0002-6600-6507, Abdulkarim, Muthanna, Adams, Jennifer Y. M., Stokniene, Joana, Francis, Lewis W., Gumbleton, Mark ORCID: https://orcid.org/0000-0002-7386-311X, Johns, Jenny, Hill, Katja E. ORCID: https://orcid.org/0000-0002-8590-0117, Jones, Adam V., Parsons, Peter G., Reddell, Paul and Thomas, David W. ORCID: https://orcid.org/0000-0001-7319-5820 2022. Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds. Science Translational Medicine 14 (662) 10.1126/scitranslmed.abn3758

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Abstract

Bacterial biofilms pose a therapeutic challenge to managing chronic wounds and contribute to antimicrobial resistance. Here, Powell et al. investigated the structure/activity relationships of epoxy-tigliane compounds derived from the blushwood tree with respect to their role in wound healing. The compounds interacted with the cell wall of bacteria but showed variable permeabilization in Gram-negative versus Gram-positive cultures. They disrupted established biofilms by interacting with the extracellular polymeric substance matrix, activated immune cells to induce reactive oxygen species, and promoted wound healing in infected thermal injuries in calves when applied topically. In chronic wounds in diabetic mice, the semisynthetic compound EBC-1013 up-regulated host-defense peptides, altered cytokine expression, activated immune cells, and led to greater wound closure. Results help uncover the mechanism by which epoxy-tiglianes promote wound healing and support further development of EBC-1013.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Biosciences Dentistry Pharmacy
Publisher:	American Association for the Advancement of Science
ISSN:	1946-6234
Date of First Compliant Deposit:	28 September 2022
Date of Acceptance:	24 August 2022
Last Modified:	05 Nov 2024 19:00
URI:	https://orca.cardiff.ac.uk/id/eprint/152941

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