دورية أكاديمية
A Toxin Involved in Salmonella Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase.
| العنوان: | A Toxin Involved in Salmonella Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase. |
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| المؤلفون: | VanDrisse CM; University of Georgia-Athens, Athens, Georgia, USA., Parks AR; University of Georgia-Athens, Athens, Georgia, USA., Escalante-Semerena JC; University of Georgia-Athens, Athens, Georgia, USA jcescala@uga.edu. |
| المصدر: | MBio [mBio] 2017 May 30; Vol. 8 (3). Date of Electronic Publication: 2017 May 30. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
| مواضيع طبية MeSH: | Toxin-Antitoxin Systems*, Antitoxins/*metabolism , Bacterial Proteins/*metabolism , Bacterial Toxins/*metabolism , Carboxylic Ester Hydrolases/*metabolism , Salmonella typhimurium/*physiology, Acetylation ; Acetyltransferases/metabolism ; Antitoxins/chemistry ; Bacterial Toxins/genetics ; Gene Expression Regulation, Bacterial ; Humans ; Hydrolases/metabolism ; Lysine/metabolism ; Salmonella typhimurium/enzymology ; Salmonella typhimurium/genetics ; Sirtuins/metabolism |
| مستخلص: | 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. (Copyright © 2017 VanDrisse et al.) |
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| معلومات مُعتمدة: | R01 GM062203 United States GM NIGMS NIH HHS |
| فهرسة مساهمة: | Keywords: CobB sirtuin deacetylase; lysine acetylation; persistence; protein acetylation; protein synthesis inhibition; type II toxin-antitoxin |
| المشرفين على المادة: | 0 (Antitoxins) 0 (Bacterial Proteins) 0 (Bacterial Toxins) EC 2.3.1.- (Acetyltransferases) EC 3.- (Hydrolases) EC 3.1.1.- (Carboxylic Ester Hydrolases) EC 3.1.1.- (CobB protein, Salmonella enterica) EC 3.5.1.- (Sirtuins) K3Z4F929H6 (Lysine) |
| تواريخ الأحداث: | Date Created: 20170601 Date Completed: 20180214 Latest Revision: 20191227 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5449658 |
| DOI: | 10.1128/mBio.00708-17 |
| PMID: | 28559487 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2150-7511 |
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| DOI: | 10.1128/mBio.00708-17 |