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

Abstract

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.

The association between Hfq and RNase E in long-term nitrogen starvedEscherichia coli

“…It is well established that rRNA becomes degraded in both N and carbon (C) starved E. coli , and this concomitantly results in a decrease in the cellular ribosome content (Dai et al ., 2016, Li et al ., 2018). Consistent with this, we recently reported that 16S and 23S rRNAs are gradually degraded over the initial 24 h under N starvation, i.e., over a period of time that coincides with H-body formation (Switzer et al ., 2020, McQuail et al ., 2020). RNase E is an important component in the rRNA degradation pathway in E. coli (Sulthana et al ., 2016).…”

“…It is conceivable that the H-bodies form to efficiently degrade untranslated mRNAs and rRNAs in N starved E. coli to release N from nitrogenous RNA molecules to maintain cellular processes as N starvation ensues. In support of this view, we recently reported that 16S and 23S rRNAs are gradually degraded over the initial 24 h under N starvation, i.e., over a period of time that coincides with H-body formation (21). Hfq is involved in the assembly of ribosomes (28) and recently it was reported that Hfq, together with the 3'-5' exoribonuclease RNase R, is involved in the degradation pathway associated with the removal of abnormal rRNA intermediates (29).…”

“…Recently we reported that, despite running out of N, E. coli cells remain transcriptionally active over the initial 24 h under N starvation (Switzer et al ., 2020), with ∼10% of the transcriptome differentially expressed (242 genes upregulated and 209 genes down regulated). Rifampicin treatment immediately following N run-out had a detrimental effect on cell viability at N-24 (∼50% reduction compared to untreated) suggesting that the transcriptional activity during the initial 24 h following N run-out is important for optimal cell viability (Switzer et al ., 2020). Rifampicin treatment will lead to the inhibition of de novo transcription and subsequent depletion of cellular RNA pool over time.…”

Taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism

“…Another important finding was the enrichment of the enzymes involved in the final purine catabolism (5-hydroxyisourate hydrolase, allantoate deiminase, and (S)-ureidoglycine aminohydrolase) in tophaceous gout patients versus healthy controls. There is evidence of an adaptive response of Escherichia-Shigella members to long-term nitrogen starvation in anaerobic environments, which requires allantoin degradation (Switzer et al 2020 ). It is worth noting that E. coli can obtain four nitrogen atoms from purines, while it can only gain one nitrogen atom from each uracil molecule through the reductive pyrimidine catabolic pathway (Salway 2018 ; Yin et al 2019 ).…”

Increasing ATP turnover boosts productivity of 2,3-butanediol synthesis in Escherichia coli

“…The control strain showed still limited growth at the beginning of the second phase (Fig. 3 ), possibly due to some intracellular nitrogen storage or/and due to alteration of the biomass composition [ 32 ]. The glucose was rapidly consumed by the ATPase strain with a high uptake rate of 9.26 mmol/(gDW·h), which is close to the uptake rate under growth and six times higher than the rate of the control strain under these conditions.…”