Biochemical, structural, and functional studies reveal that MAB_4324c from Mycobacterium abscessus is an active tandem repeat N-acetyltransferase

Husam M.A.B. Alsarraf, Kien Lam Ung, Matt D. Johansen, Juliette Dimon, Vincent Olieric, Laurent Kremer, Mickaël Blaise*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Abstract

Mycobacterium abscessus is a pathogenic non-tuberculous mycobacterium that possesses an intrinsic drug resistance profile. Several N-acetyltransferases mediate drug resistance and/or participate in M. abscessus virulence. Mining the M. abscessus genome has revealed genes encoding additional N-acetyltransferases whose functions remain uncharacterized, among them MAB_4324c. Here, we showed that the purified MAB_4324c protein is a N-acetyltransferase able to acetylate small polyamine substrates. The crystal structure of MAB_4324c was solved at high resolution in complex with its cofactor, revealing the presence of two GCN5-related N-acetyltransferase domains and a cryptic binding site for NADPH. Genetic studies demonstrate that MAB_4324c is not essential for in vitro growth of M. abscessus; however, overexpression of the protein enhanced the uptake and survival of M. abscessus in THP-1 macrophages.

Original languageEnglish
JournalFEBS Letters
Volume596
Issue12
Pages (from-to)1516-1532
Number of pages17
ISSN0014-5793
DOIs
Publication statusPublished - Jun 2022

Keywords

  • GCN5
  • infection
  • intracellular survival
  • macrophage
  • Mycobacterium abscessus
  • N-acetyltransferase
  • X-ray structure

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