A novel regulatory factor affecting the transcription of methionine biosynthesis genes in Escherichia coli experiencing sustained nitrogen starvation

Switzer, Amy; Evangelopoulos, Dimitrios; Figueira, R.C.S.; Carvalho, Luiz Pedro S. de; Brown, Daniel R.; Wigneshweraraj, Sivaramesh

doi:10.1099/mic.0.000683

Cited by 16 publications

(26 citation statements)

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“…Therefore, an exponentially growing batch culture of E. coli rapidly attenuates growth upon N run-out ( 9 – 11 ). The initial adaptive response to N run-out, the N regulation (Ntr) stress response, results in the large-scale and multilevel reprogramming of the transcriptome, involving ∼40% of all E. coli genes, to allow E. coli to adjust to N starvation ( 12 – 14 ). Since E. coli perceives N run-out as a decrease in the internal concentration of glutamine, the genes expressed as part of the Ntr response are predominantly involved in the transport and assimilation of nitrogenous compounds into glutamine or glutamate, yielding these catabolically or sparing the requirement for them in cellular processes ( 12 , 13 ).…”

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confidence: 99%

The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin

et al. 2020

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Bacteria initially respond to nutrient starvation by eliciting large-scale transcriptional changes. The accompanying changes in gene expression and metabolism allow the bacterial cells to effectively adapt to the nutrient starved state. How the transcriptome subsequently changes as nutrient starvation ensues is not well understood. We used nitrogen (N) starvation as a model nutrient starvation condition to study the transcriptional changes in Escherichia coli experiencing long-term N starvation. The results reveal that the transcriptome of N starved E. coli undergoes changes that are required to maximise chances of viability and to effectively recover growth when N starvation conditions become alleviated. We further reveal that, over time, N starved E. coli cells rely on the degradation of allantoin for optimal growth recovery when N becomes replenished. This study provides insights into the temporally coordinated adaptive responses that occur in E. coli experiencing sustained N starvation. IMPORTANCE Bacteria in their natural environments seldom encounter conditions that support continuous growth. Hence, many bacteria spend the majority of their time in states of little or no growth due to starvation of essential nutrients. To cope with prolonged periods of nutrient starvation, bacteria have evolved several strategies, primarily manifesting themselves through changes in how the information in their genes is accessed. How these coping strategies change over time under nutrient starvation is not well understood and this knowledge is not only important to broaden our understanding of bacterial cell function, but also to potentially find ways to manage harmful bacteria. This study provides insights into how nitrogen starved Escherichia coli bacteria rely on different genes during long term nitrogen starvation.

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Section: Introductionmentioning

confidence: 99%

The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin

et al. 2020

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“…As can be seen in Fig. 2E, RpoS is clearly upregulated, and RpoS-dependent gene expression has been demonstrated to be active under our N-starvation conditions (8). Therefore, I decided to determine whether RpoS plays a role in the formation of N-starvation-induced persisters.…”

Section: Resultsmentioning

confidence: 89%

“…The response also induces the further expression of genes to survive N starvation through the action of the dual regulator Nac, the nitrogen accessory control protein (6). Recently, we showed that the least understood NtrC-regulated operon, yeaGH, which encodes a putative serine/ threonine kinase and has a gene of unknown function, promotes the survival of E. coli when faced with sustained N starvation, appearing to act as a molecular brake, dampening the metabolic activity of N-starved E. coli (7,8).…”

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Nitrogen Starvation Induces Persister Cell Formation in Escherichia coli

Brown

2019

J Bacteriol

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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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“…We defined differentially expressed genes as those with expression levels changed ≥ 2-fold with a false discovery rate adjusted P-value < 0.05. As previously reported by us and others, the initial transcriptional response to N starvation involves differential expression of 1787 genes primarily required for scavenging and catabolism of alternative N sources (6, 8, 9) and thus, we did not investigate these genes further (Phase A in Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

“…The RNA-seq data set was previously generated and analysed by Switzer et al (8). The analysis of differential gene expression during NAP as well as the statistical analyses were also conducted in the same way as described previously.…”

Section: Methodsmentioning

confidence: 99%

The adaptive response to long-term nitrogen starvation inEscherichia colirequires the breakdown of allantoin

Switzer

Burchell

McQuail

et al. 2020

Preprint

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26Bacteria initially respond to conditions that attenuate their growth by eliciting large-scale 27 transcriptional changes. The accompanying changes in gene expression and metabolism allow 28 the bacterial cells to effectively adapt to the growth attenuated state. How the transcriptome 29 subsequently changes as growth attenuation ensues is not well understood. We used nitrogen 30 (N) starvation as a model nutrient starvation condition to study the transcriptome of growth 31 attenuated Escherichia coli. The results reveal that the transcriptome of nitrogen starvation-32 induced growth attenuated E. coli remains dynamic and perturbations to it compromise the 33 viability of growth attenuated bacteria and their ability to effectively recover growth when N 34 starvation conditions become alleviated. We further reveal that, over time, N starvation-35 induced growth attenuated bacteria rely on the degradation of allantoin for optimal growth 36 recovery when N becomes replenished. This study provides insights into the temporally 37 coordinated adaptive responses that occur in E. coli experiencing sustained N starvation. 38 39 IMPORTANCE 40Bacteria in their natural environments seldom encounter conditions that support continuous 41 growth. Hence, many bacteria spend the majority of their time in states of little or no growth 42 due to starvation of essential nutrients. To cope with prolonged periods of nutrient starvation, 43 bacteria have evolved several strategies, primarily manifesting themselves through changes in 44 how the information in their genes is accessed. How these coping strategies change over time 45 under nutrient starvation is not well understood and this knowledge is not only important to 46 broaden our understanding of bacterial cell function, but also to potentially find ways to 47 manage harmful bacteria. This study provides insights into how nitrogen starved Escherichia 48 coli bacteria rely on different genes during long term nitrogen starvation. 49 50 3 KEYWORDS 51

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A novel regulatory factor affecting the transcription of methionine biosynthesis genes in Escherichia coli experiencing sustained nitrogen starvation

Cited by 16 publications

References 29 publications

The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin

The Adaptive Response to Long-Term Nitrogen Starvation in Escherichia coli Requires the Breakdown of Allantoin

Nitrogen Starvation Induces Persister Cell Formation in Escherichia coli

The adaptive response to long-term nitrogen starvation inEscherichia colirequires the breakdown of allantoin

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