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Nitrogen Starvation Induces Persister Cell Formation in Escherichia coli.
Brown, Daniel R.
Afiliación
  • Brown DR; MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom drbrown@imperial.ac.uk.
J Bacteriol ; 201(3)2019 02 01.
Article en En | MEDLINE | ID: mdl-30420451
To cope with fluctuations in their environment, bacteria have evolved multiple adaptive stress responses. One such response is the nitrogen regulation stress response, which allows bacteria, such as Escherichia coli, to cope with and overcome conditions of nitrogen limitation. This response is directed by the two-component system NtrBC, where NtrC acts as the major transcriptional regulator to activate the expression of genes to mount the response. Recently, my colleagues and I showed that NtrC directly regulates the expression of the relA gene, the major (p)ppGpp synthetase in E. coli, coupling the nitrogen regulation stress and stringent responses. As elevated levels of (p)ppGpp have been implicated in the formation of persister cells, here, I investigated whether nitrogen starvation promotes their formation and whether the NtrC-RelA regulatory cascade plays a role. The results reveal that nitrogen-starved E. coli synthesizes (p)ppGpp and forms a higher percentage of persister cells than nonstarved cells and that both NtrC and RelA are important for these processes. This study provides novel insights into how the formation of persisters can be promoted in response to a nutritional stress.IMPORTANCE Bacteria often reside in environments where nutrient availability is scarce; therefore, they have evolved adaptive responses to rapidly cope with conditions of feast and famine. Understanding the mechanisms that underpin the regulation of how bacteria cope with this stress is a fundamentally important question in the wider context of understanding the biology of the bacterial cell and bacterial pathogenesis. Two major adaptive mechanisms to cope with starvation are the nitrogen regulation (ntr) stress and stringent responses. Here, I describe how these bacterial stress responses are coordinated under conditions of nitrogen starvation to promote the formation of antibiotic-tolerant persister cells by elevating levels of the secondary messenger (p)ppGpp.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Factores de Transcripción / Adaptación Fisiológica / GTP Pirofosfoquinasa / Proteínas de Escherichia coli / Escherichia coli / Proteínas PII Reguladoras del Nitrógeno / Nitrógeno Idioma: En Revista: J Bacteriol Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Estrés Fisiológico / Factores de Transcripción / Adaptación Fisiológica / GTP Pirofosfoquinasa / Proteínas de Escherichia coli / Escherichia coli / Proteínas PII Reguladoras del Nitrógeno / Nitrógeno Idioma: En Revista: J Bacteriol Año: 2019 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos