دورية أكاديمية
Intoxication of antibiotic persisters by host RNS inactivates their efflux machinery during infection.
| العنوان: | Intoxication of antibiotic persisters by host RNS inactivates their efflux machinery during infection. |
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| المؤلفون: | Séverin Ronneau, Charlotte Michaux, Rachel T Giorgio, Sophie Helaine |
| المصدر: | PLoS Pathogens, Vol 20, Iss 2, p e1012033 (2024) |
| بيانات النشر: | Public Library of Science (PLoS), 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | The host environment is of critical importance for antibiotic efficacy. By impacting bacterial machineries, stresses encountered by pathogens during infection promote the formation of phenotypic variants that are transiently insensitive to the action of antibiotics. It is assumed that these recalcitrant bacteria-termed persisters-contribute to antibiotic treatment failure and relapsing infections. Recently, we demonstrated that host reactive nitrogen species (RNS) transiently protect persisters against the action of β-lactam antibiotics by delaying their regrowth within host cells. Here, we discovered that RNS intoxication of persisters also collaterally sensitizing them to fluoroquinolones during infection, explaining the higher efficiency of fluoroquinolones against intramacrophage Salmonella. By reducing bacterial respiration and the proton-motive force, RNS inactivate the AcrAB efflux machinery of persisters, facilitating the accumulation of fluoroquinolones intracellularly. Our work shows that target inactivity is not the sole reason for Salmonella persisters to withstand antibiotics during infection, with active efflux being a major contributor to survival. Thus, understanding how the host environment impacts persister physiology is critical to optimize antibiotics efficacy during infection. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1012033&type=printable; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1012033&type=printable |
| DOI: | 10.1371/journal.ppat.1012033 |
| URL الوصول: | https://doaj.org/article/73a02194fe3e49c5bec32e0733aa8406 |
| رقم الأكسشن: | edsdoj.73a02194fe3e49c5bec32e0733aa8406 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1012033&type=printable |