Are UTIs-associated E. coli persisters linked to antibiotic resistance and tolerance?

Details

Supervisors

Van Bambeke, Françoise

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

Urinary tract infections (UTIs) are a major health problem, affecting more than 400 million people yearly. The primary cause of these infections is Uropathogenic Escherichia coli. This bacterium can be extracellular and intracellular, forming reservoirs that can cause treatment failures and recurrent infections. Recent studies suggest that recurrences are associated with persistent bacteria. These bacteria represent a dormant-like sub-population that isn’t affected by antibiotics, but reproliferate once the antibiotic is removed. In contrast, resistant bacteria will continue to grow despite the presence of antibiotic, while tolerant bacteria will die under antibiotic treatment at a slower rate than susceptible bacteria. Given that resistance, tolerance, and persistence have been associated in various cases in the literature, it seemed logical to ask the following question: Are UTIs-associated E. coli persisters linked to antibiotic resistance and tolerance? To address this question, serial passages of MIC tests and extracellular antibiotic treatments in stationary phase were performed with the native strain to select respectively resistant bacteria and hyper-persitent bacteria. To determine if there’s an influence of persistence on resistance, serial passages of MIC tests were conducted again on the hyper-persistent bacteria, and the results were compared with the results of the native strain. Conversely, to assess the influence of resistance on persistence, the extracellular antibiotic treatments in the stationary phase were executed again on the obtained resistant bacteria and the results were compared with the results of the native strain. The findings lead us to confirm that resistance has an influence on persistence with this strain by reaching a higher persister fraction faster and that persistence may have an influence on resistance for UTI89 by postponing the emergence of resistance. As it is equally important to consider the influence of persistence on tolerance, which also confers survivability to bacteria, the current experiment we are performing consists in comparing the kill curve of the native strain with the kill curve of persisters. Hypothetically, in case of a positive influence of persistence on tolerance, we would see a higher MDK99 in persistent bacteria than in the native strain, indicating a slower killing. The results lead us to the conclusions that persistence doesn’t have an influence on tolerance. And lastly, whole genome sequencing (WGS) analyses on the evolved hyper-persistent and resistant strains is still on process. They will be essential as they could bring to light key changes compared to the native strain, giving us further insight into the possible mechanisms implicated in UPEC’s survivability against antibiotic treatment.