Salmonella Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress

MBio
Liam F FitzsimmonsAndrés Vázquez-Torres

Abstract

The adaptations that protect pathogenic microorganisms against the cytotoxicity of nitric oxide (NO) engendered in the immune response are incompletely understood. We show here that salmonellae experiencing nitrosative stress suffer dramatic losses of the nucleoside triphosphates ATP, GTP, CTP, and UTP while simultaneously generating a massive burst of the alarmone nucleotide guanosine tetraphosphate. RelA proteins associated with ribosomes overwhelmingly synthesize guanosine tetraphosphate in response to NO as a feedback mechanism to transient branched-chain amino acid auxotrophies. Guanosine tetraphosphate activates the transcription of valine biosynthetic genes, thereby reestablishing branched-chain amino acid biosynthesis that enables the translation of the NO-consuming flavohemoglobin Hmp. Guanosine tetraphosphate synthesized by RelA protects salmonellae from the metabolic stress inflicted by reactive nitrogen species generated in the mammalian host response. This research illustrates the importance of nucleotide metabolism in the adaptation of salmonellae to the nutritional stress imposed by NO released in the innate host response.IMPORTANCE Nitric oxide triggers dramatic drops in nucleoside triphosphates, the building bl...Continue Reading

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Citations

Mar 5, 2019·Current Genetics·Heinrich Schäfer, Kürşad Turgay
Jul 17, 2019·The Journal of Infectious Diseases·Larisa V Gubareva, Alicia M Fry
Mar 17, 2020·PLoS Genetics·Heinrich SchäferKürşad Turgay
Mar 7, 2020·Science Advances·Jessica Jones-CarsonAndrés Vázquez-Torres
Apr 2, 2020·Journal of Bacteriology·María Pérez-VarelaPhilip Rather
Feb 27, 2020·MBio·Liam F FitzsimmonsAndres Vazquez-Torres
Nov 16, 2018·Proceedings of the National Academy of Sciences of the United States of America·Ju-Sim KimAndrés Vázquez-Torres
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Nov 10, 2020·Frontiers in Microbiology·Llorenç Fernández-Coll, Michael Cashel
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Aug 7, 2021·Frontiers in Digital Health·Allison J Lopatkin, Jason H Yang
Sep 8, 2021·Infection and Immunity·Liam F FitzsimmonsTed Hackstadt

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Methods Mentioned

BETA
in vitro transcription
GTPases
aminoacylation
PCR

Software Mentioned

SoftMax Pro
GraphPad Prism
Rad CFX Manager
ImageJ

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