Timing of bactericidal activity of fluoroquinolones against nongrowing uropathogenic Escherichia coli

Abstract

Urinary tract infections (UTIs) are among the most common bacterial infections, especially in women, and are often caused by uropathogenic Escherichia coli (UPEC). These bacteria have the ability to invade bladder cells, making them difficult to eliminate completely. In many cases, UPEC can persist in the body even after antibiotic treatment and later cause recurrent infections. Fluoroquinolones (FQs) are antibiotics that kill bacteria by damaging their DNA. Some fluoroquinolones are of particular interest because standard killing assays have shown that they can eliminate a substantial proportion of non-growing bacteria, unlike many antibiotics whose activity is largely restricted to actively growing cells. However, bacteria in a nongrowing state are often more tolerant to these drugs. Recent studies suggest that DNA damage does not occur during FQ treatment when cells are nongrowing. Instead, it occurs after the bacteria are placed in fresh, drug-free medium and begin to regrow. This suggests that fluoroquinolones may not kill nongrowing bacteria immediately but instead poison them, leading to damage and death later during recovery. This study measured the timing of SOS response activation in the uropathogenic E. coli strain CFT073 using a fluorescent reporter system. The bacteria were treated with four fluoroquinolones—ofloxacin, gatifloxacin, sitafloxacin, and norfloxacin—under growing, nongrowing, and regrowing conditions. A dual-fluorescent plasmid tracked bacterial presence and DNA damage in real time. The results showed that the SOS response was low during the treatment of nongrowing cells but increased significantly after cells resumed growth. These findings support the idea that fluoroquinolones poison nongrowing E. coli without causing immediate DNA damage, which only appears during regrowth. This has important implications for improving treatment strategies.