Reference - Detail
| RRC ID | 78980 |
|---|---|
| Author | Lorenzo Bernacchia, Arya Gupta, Antoine Paris, Alexandra A. Moores, Neil M. Kad |
| Title | Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors |
| Journal | PLOS Pathogens |
| 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 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. |
| Volume | 19 |
| Pages | e1011875 |
| Published | 2023-12-7 |
| DOI | 10.1371/journal.ppat.1011875 |
| PMID | 38060607 |
| PMC | PMC10729960 |
| MeSH | Anti-Infective Agents* Cisplatin / pharmacology Cisplatin / therapeutic use DNA Damage DNA Repair DNA, Bacterial Escherichia coli / genetics Humans Neoplasms* / drug therapy |
| IF | 6.218 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Prokaryotes E. coli | Keio collection |