التفاصيل البيبلوغرافية
| العنوان: |
In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility. |
| المؤلفون: |
Parsons, Joshua B., Sidders, Ashelyn E., Velez, Amanda Z., Hanson, Blake M., Angeles-Solano, Michelle, Ruffin, Felicia, Rowe, Sarah E., Arias, Cesar A., Fowler Jr., Vance G., Thaden, Joshua T., Conlon, Brian P. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 1/16/2024, Vol. 121 Issue 3, p1-9, 23p |
| مصطلحات موضوعية: |
GRAM-negative bacterial diseases, ESCHERICHIA coli, COUPLES therapy, ANTIBIOTICS, HYPNOTISM |
| مستخلص: |
Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using Escherichia coli clinical bloodstream isolate pairs (initial and relapse isolates) from patients with relapsed GNB-BSI, we found that 4/11 (36%) of the relapse isolates displayed a significant increase in persisters cells relative to the initial bloodstream infection isolate. In the relapsed E. coli strain with the greatest increase in persisters (100-fold relative to initial isolate), we determined that the increase was due to a loss-of- function mutation in the ptsI gene encoding Enzyme I of the phosphoenolpyruvate phosphotransferase system. The ptsI mutant was equally virulent in a murine bacteremia infection model but exhibited 10-fold increased survival to antibiotic treatment. This work addresses the controversy regarding the clinical relevance of persister formation by providing compelling data that not only do high-persister mutations arise during bloodstream infection in humans but also that these mutants display increased survival to antibiotic challenge in vivo. [ABSTRACT FROM AUTHOR] |
|
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
