Bacterial strategies for surviving antibiotics during urinary tract infection: could uropathogenic Escherichia coli be persisters?

Abstract

Treating bacterial infections, such as urinary tract infection (UTI), with antibiotics does not always resolve the infection and often results in subsequent re-infection. Treatment failure can be driven by bacterial mechanisms of resistance, tolerance or persistence, collectively known as the antibiotic non-response. Antibiotic resistance is well characterized across various bacterial species and implicated in poor clinical outcomes in various infection settings. In the instance of resistance, bacteria harbour genetic determinants to evade antibiotics and continue to grow during treatment. Notably, bacteria can escape antibiotic killing in the absence of resistance genes. In response to the environment, an entire bacterial population can slow its growth rate, becoming tolerant to bactericidal antibiotic exposure. Alternatively, a subpopulation of bacteria, known as persister cells, survive whereas the remainder of the population is eliminated by bactericidal antibiotics. Both mechanisms enable bacteria to survive treatment, with the capacity to regrow following cessation of antibiotic treatment. However, our understanding of tolerance and persistence in the context of UTI is limited. Thus, two bacterial phenotypes that might contribute to poor outcomes are overlooked both in the clinic and in research, which could add to the challenges of treatment failure and recurrent UTI.