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Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors

Bernacchia, Lorenzo, Gupta, Arya, Paris, Antoine, Moores, Alexandra A., Kad, Neil M (2023) Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. PLoS Pathogens, 19 (12). Article Number e1011875. ISSN 1553-7374. (doi:10.1371/journal.ppat.1011875) (KAR id:104465)

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Cancer chemotherapeutics kill rapidly dividing cells, which includes cells of the immune system. The resulting neutropenia predisposes patients to infection, which delays treatment and is a major cause of morbidity and mortality. To tackle this problem, we have isolated several compounds that inhibit bacterial DNA repair, alone they are non-toxic, however in combination with DNA damaging anti-cancer drugs, they prevent bacterial growth. These compounds were identified through screening of an FDA-approved drug library in the presence of the anti-cancer compound cisplatin. Using a series of triage tests, the screen was reduced to a handful of drugs that were tested for specific activity against bacterial nucleotide excision DNA repair (NER). Five compounds emerged, of which three possess promising antimicrobial properties including cell penetrance, and the ability to block replication in a multi-drug resistant clinically relevant E. coli strain. This study suggests that targeting NER could offer a new therapeutic approach tailor-made for infections in cancer patients, by combining cancer chemotherapy with an adjuvant that targets DNA repair.

Item Type: Article
DOI/Identification number: 10.1371/journal.ppat.1011875
Projects: Hijacking chemotherapy to overcome microbial infection during cancer treatment
Additional information: For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (
Cancer Research UK (
Medical Research Council (
Depositing User: Neil Kad
Date Deposited: 02 Jan 2024 15:53 UTC
Last Modified: 21 Feb 2024 16:12 UTC
Resource URI: (The current URI for this page, for reference purposes)

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