Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>

ABSTRACT In Salmonella enterica, the reversible lysine acetylation (RLA) system is comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB). RLA controls the activities of many proteins, including the acetyl coenzyme A (acetyl-CoA) synthetase (Acs), by modulating the degree of...

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Autores principales:	Kristy L. Hentchel, Sandy Thao, Peter J. Intile, Jorge C. Escalante-Semerena
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e8cb9fced4a7495698ef3197fab45eb2
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spelling	oai:doaj.org-article:e8cb9fced4a7495698ef3197fab45eb22021-11-15T15:41:27ZDeciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>10.1128/mBio.00891-152150-7511https://doaj.org/article/e8cb9fced4a7495698ef3197fab45eb22015-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00891-15https://doaj.org/toc/2150-7511ABSTRACT In Salmonella enterica, the reversible lysine acetylation (RLA) system is comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB). RLA controls the activities of many proteins, including the acetyl coenzyme A (acetyl-CoA) synthetase (Acs), by modulating the degree of Acs acetylation. We report that IolR, a myo-inositol catabolism repressor, activates the expression of genes encoding components of the RLA system. In vitro evidence shows that the IolR protein directly regulates pat expression. An iolR mutant strain displayed a growth defect in minimal medium containing 10 mM acetate, a condition under which RLA function is critical to control Acs activity. Increased levels of Pat, CobB, or Acs activity reversed the growth defect, suggesting the Pat/CobB ratio in an iolR strain is altered and that such a change affects the level of acetylated, inactive Acs. Results of quantitative reverse transcription-PCR (qRT-PCR) analyses of pat, cobB, and acs expression indicated that expression of the genes alluded to in the IolR-deficient strain was reduced 5-, 3-, and 2.6-fold, respectively, relative to the levels present in the strain carrying the iolR+ allele. Acs activity in cell-free extracts from an iolR mutant strain was reduced ~25% relative to that of the iolR+ strain. Glucose differentially regulated expression of pat, cobB, and acs. The catabolite repressor protein (Crp) positively regulated expression of pat while having no effect on cobB. IMPORTANCE Reversible lysine acylation is used by cells of all domains of life to modulate the function of proteins involved in diverse cellular processes. Work reported herein begins to outline the regulatory circuitry that integrates the expression of genes encoding enzymes that control the activity of a central metabolic enzyme in C2 metabolism. Genetic analyses revealed effects on reversible lysine acylation that greatly impacted the growth behavior of the cell. This work provides the first insights into the complexities of the system responsible for controlling reversible lysine acylation at the transcriptional level in the enteropathogenic bacterium Salmonella enterica.Kristy L. HentchelSandy ThaoPeter J. IntileJorge C. Escalante-SemerenaAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 4 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Kristy L. Hentchel Sandy Thao Peter J. Intile Jorge C. Escalante-Semerena Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>
description	ABSTRACT In Salmonella enterica, the reversible lysine acetylation (RLA) system is comprised of the protein acetyltransferase (Pat) and sirtuin deacetylase (CobB). RLA controls the activities of many proteins, including the acetyl coenzyme A (acetyl-CoA) synthetase (Acs), by modulating the degree of Acs acetylation. We report that IolR, a myo-inositol catabolism repressor, activates the expression of genes encoding components of the RLA system. In vitro evidence shows that the IolR protein directly regulates pat expression. An iolR mutant strain displayed a growth defect in minimal medium containing 10 mM acetate, a condition under which RLA function is critical to control Acs activity. Increased levels of Pat, CobB, or Acs activity reversed the growth defect, suggesting the Pat/CobB ratio in an iolR strain is altered and that such a change affects the level of acetylated, inactive Acs. Results of quantitative reverse transcription-PCR (qRT-PCR) analyses of pat, cobB, and acs expression indicated that expression of the genes alluded to in the IolR-deficient strain was reduced 5-, 3-, and 2.6-fold, respectively, relative to the levels present in the strain carrying the iolR+ allele. Acs activity in cell-free extracts from an iolR mutant strain was reduced ~25% relative to that of the iolR+ strain. Glucose differentially regulated expression of pat, cobB, and acs. The catabolite repressor protein (Crp) positively regulated expression of pat while having no effect on cobB. IMPORTANCE Reversible lysine acylation is used by cells of all domains of life to modulate the function of proteins involved in diverse cellular processes. Work reported herein begins to outline the regulatory circuitry that integrates the expression of genes encoding enzymes that control the activity of a central metabolic enzyme in C2 metabolism. Genetic analyses revealed effects on reversible lysine acylation that greatly impacted the growth behavior of the cell. This work provides the first insights into the complexities of the system responsible for controlling reversible lysine acylation at the transcriptional level in the enteropathogenic bacterium Salmonella enterica.
format	article
author	Kristy L. Hentchel Sandy Thao Peter J. Intile Jorge C. Escalante-Semerena
author_facet	Kristy L. Hentchel Sandy Thao Peter J. Intile Jorge C. Escalante-Semerena
author_sort	Kristy L. Hentchel
title	Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>
title_short	Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>
title_full	Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>
title_fullStr	Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>
title_full_unstemmed	Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>
title_sort	deciphering the regulatory circuitry that controls reversible lysine acetylation in <named-content content-type="genus-species">salmonella enterica</named-content>
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/e8cb9fced4a7495698ef3197fab45eb2
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Deciphering the Regulatory Circuitry That Controls Reversible Lysine Acetylation in <named-content content-type="genus-species">Salmonella enterica</named-content>

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