(p)ppGpp-mediated stress response induced by defects in outer membrane biogenesis and ATP production promotes survival in Escherichia coli

Scientific Reports
Mohammad RoghanianFarshid Jalalvand

Abstract

Cellular growth requires a high level of coordination to ensure that all processes run in concert. The role of the nucleotide alarmone (p)ppGpp has been extensively studied in response to external stresses, such as amino acid starvation, in Escherichia coli, but much less is known about the involvement of (p)ppGpp in response to perturbations in intracellular processes. We therefore employed CRISPRi to transcriptionally repress essential genes involved in 14 vital processes and investigated whether a (p)ppGpp-mediated response would be induced. We show that (p)ppGpp is produced and required for a pertinent stress response during interference with outer membrane biogenesis and ADP synthesis specifically. When these processes were perturbed via the transcriptional repression of essential genes, wild type E. coli MG1655 ceased growing and entered a semi-dormant state, whereas isogenic (p)ppGpp0 cells continued to grow uncontrollably to the point of lysis. Furthermore, in vivo measurements revealed that the ATP levels were intrinsically offset in (p)ppGpp0 cells, further indicating a role for the alarmone in cellular energy homeostasis. In summary, our investigation suggests that (p)ppGpp acts as a coordinator of cell growth in res...Continue Reading

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Citations

Feb 2, 2020·NPJ Biofilms and Microbiomes·Hey-Min Kim, Mary E Davey
Jan 31, 2021·Current Microbiology·Alya El MayAhmed Landoulsi
Nov 10, 2020·Frontiers in Microbiology·Llorenç Fernández-Coll, Michael Cashel
Nov 6, 2020·Nature Reviews. Microbiology·Sophie E IrvingRebecca M Corrigan
Mar 13, 2021·Microbial Biotechnology·Adrian J JervisNigel S Scrutton
Jun 15, 2021·EcoSal Plus·Nicholas Backes, Gregory J Phillips
Jun 8, 2021·Antimicrobial Agents and Chemotherapy·L G KavanaughT R Steck

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Methods Mentioned

BETA
GTPase
aminoacylation
fluorescence microscopy
PCR

Software Mentioned

Nikon NIS Elements

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