Topic
Stringent response
About: Stringent response is a research topic. Over the lifetime, 1200 publications have been published within this topic receiving 60065 citations. The topic is also known as: Stringent response.
Papers published on a yearly basis
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Papers
TL;DR: A model in which M. tuberculosis arrests growth, decreases its respiration rate and is resistant to isoniazid, rifampicin and metronidazole is established, which is generated a model with which to search for agents active against persistent M.culosis.
Abstract: The search for new TB drugs that rapidly and effectively sterilize the tissues and are thus able to shorten the duration of chemotherapy from the current 6 months has been hampered by a lack of understanding of the metabolism of the bacterium when in a 'persistent' or latent form. Little is known about the condition in which the bacilli survive, although laboratory models have shown that Mycobacterium tuberculosis can exist in a non-growing, drug-resistant state that may mimic persistence in vivo. Using nutrient starvation, we have established a model in which M. tuberculosis arrests growth, decreases its respiration rate and is resistant to isoniazid, rifampicin and metronidazole. We have used microarray and proteome analysis to investigate the response of M. tuberculosis to nutrient starvation. Proteome analysis of 6-week-starved cultures revealed the induction of several proteins. Microarray analysis enabled us to monitor gene expression during adaptation to nutrient starvation and confirmed the changes seen at the protein level. This has provided evidence for slowdown of the transcription apparatus, energy metabolism, lipid biosynthesis and cell division in addition to induction of the stringent response and several other genes that may play a role in maintaining long-term survival within the host. Thus, we have generated a model with which we can search for agents active against persistent M. tuberculosis and revealed a number of potential targets expressed under these conditions.
1,465 citations
TL;DR: (p)ppGpp can contribute to regulation of many aspects of microbial cell biology that are sensitive to changing nutrient availability: growth, adaptation, secondary metabolism, survival, persistence, cell division, motility, biofilms, development, competence, and virulence.
Abstract: The fundamental details of how nutritional stress leads to elevating (p)ppGpp are questionable. By common usage, the meaning of the stringent response has evolved from the specific response to (p)ppGpp provoked by amino acid starvation to all responses caused by elevating (p)ppGpp by any means. Different responses have similar as well as dissimilar positive and negative effects on gene expression and metabolism. The different ways that different bacteria seem to exploit their capacities to form and respond to (p)ppGpp are already impressive despite an early stage of discovery. Apparently, (p)ppGpp can contribute to regulation of many aspects of microbial cell biology that are sensitive to changing nutrient availability: growth, adaptation, secondary metabolism, survival, persistence, cell division, motility, biofilms, development, competence, and virulence. Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains.
1,110 citations
TL;DR: The experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells, and inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.
Abstract: Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.
953 citations
TL;DR: This Review summarizes recent insights on the molecular mechanisms governing the activity of the RelA/SpoT homologue (RSH) proteins, which are key players that regulate the cellular levels of (p)ppGpp.
Abstract: The alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p) ppGpp) are involved in regulating growth and several different stress responses in bacteria. In ...
789 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 9 |
| 2024 | 10 |
| 2023 | 28 |
| 2022 | 51 |
| 2021 | 53 |
| 2020 | 85 |