Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors.
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 inhibi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011875&type=printable |
| _version_ | 1797370865571069952 |
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| author | Lorenzo Bernacchia Arya Gupta Antoine Paris Alexandra A Moores Neil M Kad |
| author_facet | Lorenzo Bernacchia Arya Gupta Antoine Paris Alexandra A Moores Neil M Kad |
| author_sort | Lorenzo Bernacchia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T18:11:30Z |
| format | Article |
| id | doaj.art-6ccff596be6c4e75b2730fa136e3cb2f |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-03-08T18:11:30Z |
| publishDate | 2023-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-6ccff596be6c4e75b2730fa136e3cb2f2024-01-01T05:31:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-12-011912e101187510.1371/journal.ppat.1011875Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors.Lorenzo BernacchiaArya GuptaAntoine ParisAlexandra A MooresNeil M KadCancer 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011875&type=printable |
| spellingShingle | Lorenzo Bernacchia Arya Gupta Antoine Paris Alexandra A Moores Neil M Kad Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. PLoS Pathogens |
| title | Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. |
| title_full | Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. |
| title_fullStr | Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. |
| title_full_unstemmed | Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. |
| title_short | Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors. |
| title_sort | developing novel antimicrobials by combining cancer chemotherapeutics with bacterial dna repair inhibitors |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011875&type=printable |
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