A xanthone-derived antibiotic with a multifaceted mode of action

Orababa, Oluwatosin ORCID: https://orcid.org/0000-0002-8905-9927 and Galleh, Raphael ORCID: https://orcid.org/0000-0003-2541-4851 (2025) A xanthone-derived antibiotic with a multifaceted mode of action. Nature Microbiology . Full text not available from this repository.

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Abstract

Bacterial resistance to available antibiotics continues to pose a great challenge to the successful treatment of infections. In 2019, there were close to five million annual deaths associated with antimicrobial resistance globally, and this has been predicted to rise to 10 million deaths by 2050 if nothing is done to mitigate this ‘silent pandemic’1. In addition to the misuse of currently available antibiotics, the issue of antimicrobial resistance has been further complicated by the paucity of new antimicrobials with unique mechanisms of action. Hence, the development of novel antimicrobials, for example from natural products, with broad-spectrum activity against Gram-negative and Gram-positive pathogenic bacteria is needed. Currently, only a small proportion of new antibiotics in development are effective against Gram-negative bacteria, highlighting the urgent need for the development of new antimicrobials with high potency against these resistant strains. Towards this goal, in a recent study published in Science Advances, Li et al. synthesized a broad-spectrum xanthone derivative with multiple mechanisms of action and reduced risk of resistance. Xanthones (9H-xanthen-9-one) are natural products that are produced by plants, fungi and algae, with an oxygen-containing dibenzo-γ-pyrone heterocyclic scaffold2. One of the most studied xanthones is α-mangostin, a natural product from the pericarp, bark or dried sap of mangosteen. Previously, α-mangostin has been shown to have good antibacterial activity against Gram-positive bacteria but low activity against Gram-negative bacteria. This xanthone is also associated with high production costs and high haemolytic activity. Furthermore, little is known about the mechanism of action of this xanthone against bacterial pathogens. Consequently, Li et al. aimed to design xanthone derivatives with potent activity against both Gram-positive and negative bacteria. Owing to the limited understanding of the mode of action of xanthones, Li et al. also set out to determine the mechanisms of action of these xanthone derivatives.

Item Type:	Article
Journal / Publication Title:	Nature Microbiology
Publisher:	Nature Research
ISSN:	2058-5276
Departments:	Institute of Science and Environment > STEM
Additional Information:	Dr Raphael Peter Galleh, Lecturer in Biomedical Science, University of Cumbria, UK. Oluwatosin Q. Orababa, University of Warwick, UK.
Depositing User:	Anna Lupton
Date Deposited:	23 Jun 2025 08:32
Last Modified:	23 Jun 2025 08:32
URI:	https://insight.cumbria.ac.uk/id/eprint/8933