A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase

ABSTRACT Bacterial toxin-antitoxin systems trigger the onset of a persister state by inhibiting essential cellular processes. The TacT toxin of Salmonella enterica is known to induce a persister state in macrophages through the acetylation of aminoacyl-tRNAs. Here, we show that the TacT toxin and th...

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Autores principales:	Chelsey M. VanDrisse, Anastacia R. Parks, Jorge C. Escalante-Semerena
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	CobB sirtuin deacetylase lysine acetylation persistence protein acetylation protein synthesis inhibition type II toxin-antitoxin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c5e70a5bfe6342799afbe9c6c8e54e6e
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spelling	oai:doaj.org-article:c5e70a5bfe6342799afbe9c6c8e54e6e2021-11-15T15:51:29ZA Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase10.1128/mBio.00708-172150-7511https://doaj.org/article/c5e70a5bfe6342799afbe9c6c8e54e6e2017-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00708-17https://doaj.org/toc/2150-7511ABSTRACT Bacterial toxin-antitoxin systems trigger the onset of a persister state by inhibiting essential cellular processes. The TacT toxin of Salmonella enterica is known to induce a persister state in macrophages through the acetylation of aminoacyl-tRNAs. Here, we show that the TacT toxin and the TacA antitoxin work as a complex that modulates TacT activity via the acetylation state of TacA. TacT acetylates TacA at residue K44, a modification that is removed by the NAD+-dependent CobB sirtuin deacetylase. TacA acetylation increases the activity of TacT, downregulating protein synthesis. TacA acetylation altered binding to its own promoter, although this did not change tacAT expression levels. These claims are supported by results from in vitro protein synthesis experiments used to monitor TacT activity, in vivo growth analyses, electrophoretic mobility shift assays, and quantitative reverse transcription-PCR (RT-qPCR) analysis. TacT is the first example of a Gcn5-related N-acetyltransferase that modifies nonprotein and protein substrates. IMPORTANCE During host infection, pathogenic bacteria can modulate their physiology to evade host defenses. Some pathogens use toxin-antitoxin systems to modulate a state of self-toxicity that can decrease their cellular activity, triggering the onset of a persister state. The lower metabolic activity of persister cells allows them to escape host defenses and antibiotic treatments. Hence a better understanding of the mechanisms used by pathogens to ingress and egress the persister state is of relevance to human health.Chelsey M. VanDrisseAnastacia R. ParksJorge C. Escalante-SemerenaAmerican Society for MicrobiologyarticleCobB sirtuin deacetylaselysine acetylationpersistenceprotein acetylationprotein synthesis inhibitiontype II toxin-antitoxinMicrobiologyQR1-502ENmBio, Vol 8, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	CobB sirtuin deacetylase lysine acetylation persistence protein acetylation protein synthesis inhibition type II toxin-antitoxin Microbiology QR1-502
spellingShingle	CobB sirtuin deacetylase lysine acetylation persistence protein acetylation protein synthesis inhibition type II toxin-antitoxin Microbiology QR1-502 Chelsey M. VanDrisse Anastacia R. Parks Jorge C. Escalante-Semerena A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase
description	ABSTRACT Bacterial toxin-antitoxin systems trigger the onset of a persister state by inhibiting essential cellular processes. The TacT toxin of Salmonella enterica is known to induce a persister state in macrophages through the acetylation of aminoacyl-tRNAs. Here, we show that the TacT toxin and the TacA antitoxin work as a complex that modulates TacT activity via the acetylation state of TacA. TacT acetylates TacA at residue K44, a modification that is removed by the NAD+-dependent CobB sirtuin deacetylase. TacA acetylation increases the activity of TacT, downregulating protein synthesis. TacA acetylation altered binding to its own promoter, although this did not change tacAT expression levels. These claims are supported by results from in vitro protein synthesis experiments used to monitor TacT activity, in vivo growth analyses, electrophoretic mobility shift assays, and quantitative reverse transcription-PCR (RT-qPCR) analysis. TacT is the first example of a Gcn5-related N-acetyltransferase that modifies nonprotein and protein substrates. IMPORTANCE During host infection, pathogenic bacteria can modulate their physiology to evade host defenses. Some pathogens use toxin-antitoxin systems to modulate a state of self-toxicity that can decrease their cellular activity, triggering the onset of a persister state. The lower metabolic activity of persister cells allows them to escape host defenses and antibiotic treatments. Hence a better understanding of the mechanisms used by pathogens to ingress and egress the persister state is of relevance to human health.
format	article
author	Chelsey M. VanDrisse Anastacia R. Parks Jorge C. Escalante-Semerena
author_facet	Chelsey M. VanDrisse Anastacia R. Parks Jorge C. Escalante-Semerena
author_sort	Chelsey M. VanDrisse
title	A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase
title_short	A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase
title_full	A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase
title_fullStr	A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase
title_full_unstemmed	A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase
title_sort	toxin involved in <italic toggle="yes">salmonella</italic> persistence regulates its activity by acetylating its cognate antitoxin, a modification reversed by cobb sirtuin deacetylase
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/c5e70a5bfe6342799afbe9c6c8e54e6e
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A Toxin Involved in <italic toggle="yes">Salmonella</italic> Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase

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