<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress

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,...

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Autores principales:	Liam F. Fitzsimmons, Lin Liu, Ju-Sim Kim, Jessica Jones-Carson, Andrés Vázquez-Torres
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Salmonella adaptive resistance animal models cellular redox status guanosine tetraphosphate nitric oxide Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e70262d1e4464f18940b82b2eee017e3
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spelling	oai:doaj.org-article:e70262d1e4464f18940b82b2eee017e32021-11-15T15:53:25Z<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress10.1128/mBio.00211-182150-7511https://doaj.org/article/e70262d1e4464f18940b82b2eee017e32018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00211-18https://doaj.org/toc/2150-7511ABSTRACT 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 blocks that power DNA replication; RNA transcription; translation; cell division; and the biosynthesis of fatty acids, lipopolysaccharide, and peptidoglycan. Concomitantly, this diatomic gas stimulates a burst of guanosine tetraphosphate. Global changes in nucleotide metabolism may contribute to the potent bacteriostatic activity of nitric oxide. In addition to inhibiting numerous growth-dependent processes, guanosine tetraphosphate positively regulates the transcription of branched-chain amino acid biosynthesis genes, thereby facilitating the translation of antinitrosative defenses that mediate recovery from nitrosative stress.Liam F. FitzsimmonsLin LiuJu-Sim KimJessica Jones-CarsonAndrés Vázquez-TorresAmerican Society for MicrobiologyarticleSalmonellaadaptive resistanceanimal modelscellular redox statusguanosine tetraphosphatenitric oxideMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Salmonella adaptive resistance animal models cellular redox status guanosine tetraphosphate nitric oxide Microbiology QR1-502
spellingShingle	Salmonella adaptive resistance animal models cellular redox status guanosine tetraphosphate nitric oxide Microbiology QR1-502 Liam F. Fitzsimmons Lin Liu Ju-Sim Kim Jessica Jones-Carson Andrés Vázquez-Torres <italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress
description	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 blocks that power DNA replication; RNA transcription; translation; cell division; and the biosynthesis of fatty acids, lipopolysaccharide, and peptidoglycan. Concomitantly, this diatomic gas stimulates a burst of guanosine tetraphosphate. Global changes in nucleotide metabolism may contribute to the potent bacteriostatic activity of nitric oxide. In addition to inhibiting numerous growth-dependent processes, guanosine tetraphosphate positively regulates the transcription of branched-chain amino acid biosynthesis genes, thereby facilitating the translation of antinitrosative defenses that mediate recovery from nitrosative stress.
format	article
author	Liam F. Fitzsimmons Lin Liu Ju-Sim Kim Jessica Jones-Carson Andrés Vázquez-Torres
author_facet	Liam F. Fitzsimmons Lin Liu Ju-Sim Kim Jessica Jones-Carson Andrés Vázquez-Torres
author_sort	Liam F. Fitzsimmons
title	<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress
title_short	<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress
title_full	<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress
title_fullStr	<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress
title_full_unstemmed	<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress
title_sort	<italic toggle="yes">salmonella</italic> reprograms nucleotide metabolism in its adaptation to nitrosative stress
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/e70262d1e4464f18940b82b2eee017e3
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<italic toggle="yes">Salmonella</italic> Reprograms Nucleotide Metabolism in Its Adaptation to Nitrosative Stress

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