Francisella DnaK Inhibits Tissue-nonspecific Alkaline Phosphatase

Arulanandam, Bernard P.; Chetty, Senthilnath Lakshmana; Yu, Jieh Juen; Leonard, Sean; Klose, Karl K.; Seshu, J.; Cap, Andrew; Valdés, James J.; Chambers, James P.

doi:10.1074/jbc.m112.404400

Cited by 6 publications

(1 citation statement)

References 40 publications

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“…Some newly synthesized proteins require posttranslational ATP-dependent folding, which is performed by the chaperones of the HSP family. Previously, it has been shown that chaperones of HSP families are not only important for Francisella biology but also affect the host immune response through participation in pathogenesis , and intracellular survival within the host cell . The Francisella genome encodes 9 HSP families, many of which were identified as responders to heat shock and oxidative stress .…”

Section: Resultsmentioning

confidence: 99%

Proteome Wide Profiling of N-ε-Lysine Acetylation Reveals a Novel Mechanism of Regulation of the Chitinase Activity in Francisella novicida

et al. 2020

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Francisella tularensis is a Gram-negative bacterium that causes the zoonotic disease tularemia. The historical development of tularemia as a biological weapon has led to it being characterized by the CDC as a category A biothreat agent. Neither posttranslational modification (PTM) of proteins, in particular lysine acetylation, in Francisella nor its subsequent regulation of the protein activity has been well studied. In this work, we analyze N-ε-lysine acetylation of the F. tularensis ssp. novicida proteome by mass spectrometry for the first time. To create a comprehensive acetylation profile, we enriched protein acetylation using two approaches: (1) the addition of glucose or acetate into the culture medium and (2) direct chemical acetylation of N-ε-lysines with acetyl phosphate. We discovered 280 acetylated proteins with 1178 acetylation sites in the F. tularensis ssp. novicida strain U112. Lysine acetylation is an important PTM that regulates multiple cellular processes in bacteria, including metabolism, transcription, translation, stress response, and protein folding. We discovered that Francisella chitinases A and B are acetylated naturally and when chemically induced by acetyl phosphate. Moreover, chemical overacetylation of chitinases results in silencing of the enzymatic activity. Our findings suggest a novel mechanism of posttranslational regulation of the chitinase activity and that acetylation may play a role in Francisella’s regulation of the protein activity.

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