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

ABSTRACT: 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 pro

SUBMITTER: Bernacchia L 

PROVIDER: S-EPMC10729960 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature