Sirvi Märksõna "antibiotic tolerance" järgi

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Role of the stringent response in antibiotic tolerance of Escherichia coli
(Tartu Ülikool, 2016) Alves Oliveira, Sofia Raquel; Hauryliuk, Vasili; Varik, Vallo; Tartu Ülikool. Loodus- ja täppisteaduste valdkond
The stringent response is a near-universal bacterial adaptation system control mediated by accumulation of two guanine nucleotides ppGpp and pppGpp, collectively known as (p)ppGpp. The response monitors several environmental stress inputs, such as nutrient limitation and heat shock and remodels bacterial physiology in order to overcome the challenges. In Echerichia coli (p)ppGpp levels controlled by two enzymes – RelA and SpoT, the namesakes of RelA SpoT Homologue (RSH) protein family. The stringent response is associated to induction of virulence, antibiotic resistance and was recently suggested to be the driving force behind the formation of so-called persister cells – antibiotictolerant phenotypic variants in antibiotic-sensitive population. Since drug resistance and tolerance constitute a significant public health threat, understanding the connection amongst (p)ppGpp, antibiotic treatment and persistence is of great importance.
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Susceptibility of nongrowing uropathogenic Escherichia coli to fluoroquinolones: killing and induction of the SOS response
(Tartu Ülikool, 2023) Akulich, Anna; Kaldalu, Niilo, juhendaja; Hinnu, Mariliis, juhendaja
Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections. UPEC is capable of entering the host cells and adapting to an intracellular lifestyle. This provides bacteria protection against host defensive mechanisms and antibiotics, leading to chronic and recurrent infections. Due to the limited nutrients inside host cells, bacteria are nongrowing. Nongrowing bacteria are not killed by most bactericidal antibiotics. However, some antibiotics of the fluoroquinolone group - gatifloxacin and ofloxacin – are known to be effective. According to an unpublished study, it was suggested that fluoroquinolones do not kill nongrowing bacteria but poison them. This study investigated the killing efficiency and in-duction of SOS response by a set of different fluoroquinolones in various growth conditions. Specifically, bactericidal effect on stationary phase culture before and after 1M NaCl incubation and induction of SOS response for growing stationary phase and regrowing cultures. The results of this thesis have supported the hypothesis of delayed bacterial death after fluoroquinolone poisoning.
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Timing of bactericidal activity of fluoroquinolones against nongrowing uropathogenic Escherichia coli
(Tartu Ülikool, 2026) Akulich, Anna; Kaldalu, Niilo, juhendaja
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.