Journal
FEBS LETTERS
Volume 596, Issue 12, Pages 1516-1532Publisher
WILEY
DOI: 10.1002/1873-3468.14360
Keywords
GCN5; infection; intracellular survival; macrophage; Mycobacterium abscessus; N-acetyltransferase; X-ray structure
Funding
- Fondation pour la Recherche Medicale (FRM) [DEQ20150331719]
- Lundbeck Foundation, Denmark [R303-2018-2964]
- National Research Agency [ANR-17-CE11-0008-01MyTraM]
- Labex EpiGenMed, an Investissements d'Avenir program [ANR-10-LABX-12-01]
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The study found that there are additional N-acetyltransferase genes in the genome of Mycobacterium abscessus with unclear functions. The research showed that MAB_4324c is an N-acetyltransferase capable of acetylating polyamine substrates and demonstrated its enhanced role in the uptake and survival of M. abscessus.
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.
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