Control of a chemical chaperone by a universally conserved ATPase

Summary

The universally conserved YchF/Ola1 ATPases regulate stress response pathways in prokaryotes and eukaryotes. Deletion of YchF/Ola1 leads to increased resistance against environmental stressors, such as reactive oxygen species, while their upregulation is associated with tumorigenesis in humans. The current study shows that in E. coli, the absence of YchF stimulates the synthesis of the alternative sigma factor RpoS by a transcription-independent mechanism. Elevated levels of RpoS then enhance the transcription of major stress-responsive genes. In addition, the deletion of ychF increases the levels of polyphosphate kinase, which in turn boosts the production of the evolutionary conserved and ancient chemical chaperone polyphosphate. This potentially provides a unifying concept for the increased stress resistance in bacteria and eukaryotes upon YchF/Ola1 deletion. Intriguingly, the simultaneous deletion of ychF and the polyphosphate-degrading enzyme exopolyphosphatase causes synthetic lethality in E. coli, demonstrating that polyphosphate production needs to be fine-tuned to prevent toxicity.

Graphical abstract

Highlights

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  The universally conserved ATPase YchF inhibits synthesis of RpoS and polyphosphate kinase (PPK)

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  Upon depletion of YchF, the levels of the chemical chaperone polyphosphate increase

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  Increased RpoS and polyphosphate levels explain stress resistance of Δ ychF cells

Abstract

Applied sciences; Biotechnology; Medical biochemistry