A Toxin Involved in Salmonella Persistence Regulates Its Activity by Acetylating Its Cognate Antitoxin, a Modification Reversed by CobB Sirtuin Deacetylase

mBio. 2017 May 30;8(3):e00708-17. doi: 10.1128/mBio.00708-17.


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.

Keywords: CobB sirtuin deacetylase; lysine acetylation; persistence; protein acetylation; protein synthesis inhibition; type II toxin-antitoxin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism
  • Antitoxins / chemistry
  • Antitoxins / metabolism*
  • Bacterial Proteins / metabolism*
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism*
  • Carboxylic Ester Hydrolases / metabolism*
  • Gene Expression Regulation, Bacterial
  • Humans
  • Hydrolases / metabolism
  • Lysine / metabolism
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / physiology*
  • Sirtuins / metabolism
  • Toxin-Antitoxin Systems*


  • Antitoxins
  • Bacterial Proteins
  • Bacterial Toxins
  • Acetyltransferases
  • Hydrolases
  • Carboxylic Ester Hydrolases
  • CobB protein, Salmonella enterica
  • Sirtuins
  • Lysine