Fatty acid starvation activates RelA by depleting lysine precursor pyruvate

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Bacteria undergoing nutrient starvation induce the ubiquitous stringent response, resulting in gross physiological changes that reprograms cell metabolism from fast to slow growth. The stringent response is mediated by the secondary messengers pppGpp and ppGpp collectively referred to as (p)ppGpp or "alarmone". In Escherichia coli, two paralogs, RelA and SpoT, synthesize (p)ppGpp. RelA is activated by amino acid starvation whereas SpoT, which can also degrade (p)ppGpp, responds to fatty acid (FA), carbon and phosphate starvation. Here, we discover that FA starvation leads to rapid activation of RelA and reveal the underlying mechanism. We show that fatty acid starvation leads to depletion of lysine that, in turn, leads to the accumulation of uncharged tRNALys and activation of RelA. SpoT was also activated by fatty acid starvation but to a lower level and with a delayed kinetics. Next, we discovered that pyruvate, a precursor of lysine, is depleted by FA starvation. We also propose a mechanism that explains how FA starvation leads to pyruvate depletion. Together our results raise the possibility that RelA may be a major player under many starvation conditions previously thought to depend principally on SpoT. Interestingly, FA starvation provoked a ~100-fold increase in relA dependent ampicillin tolerance. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
TidsskriftMolecular Microbiology
Vol/bind112
Udgave nummer4
Sider (fra-til)1339-1349
ISSN0950-382X
DOI
StatusUdgivet - 2019

ID: 226222540