NirD curtails the stringent response by inhibiting RelA activity in Escherichia coli

eLife

Etienne Maisonneuve¹  Paul Guiraud¹  Elsa Germain¹  Loïc Léger¹  Deborah Byrne² 

[1] Laboratoire de Chimie Bactérienne, Institut de Microbiologie de la Méditerranée, CNRS-Aix Marseille Univ (UMR7283), Marseille, France;Protein Expression Facility, Institut de Microbiologie de la Méditerranée, CNRS-Aix Marseille Univ, Marseille, France;

关键词: stringent response;    RelA;    NirD;    (p)ppGpp;    bacterial stress response;    E. coli;   

DOI  :  10.7554/eLife.64092

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Bacteria regulate their metabolism to adapt and survive adverse conditions, in particular to stressful downshifts in nutrient availability. These shifts trigger the so-called stringent response, coordinated by the signaling molecules guanosine tetra and pentaphosphate collectively referred to as (p)ppGpp. In Escherichia coli, accumulation of theses alarmones depends on the (p)ppGpp synthetase RelA and the bifunctional (p)ppGpp synthetase/hydrolase SpoT. A tight regulation of these intracellular activities is therefore crucial to rapidly adjust the (p)ppGpp levels in response to environmental stresses but also to avoid toxic consequences of (p)ppGpp over-accumulation. In this study, we show that the small protein NirD restrains RelA-dependent accumulation of (p)ppGpp and can inhibit the stringent response in E. coli. Mechanistically, our in vivo and in vitro studies reveal that NirD directly binds the catalytic domains of RelA to balance (p)ppGpp accumulation. Finally, we show that NirD can control RelA activity by directly inhibiting the rate of (p)ppGpp synthesis.

【 授权许可】

CC BY