Title :

Multiple Mycobacterium abscessus O-acetyltransferases influence glycopeptidolipid structure and colony morphotype.

Author(s) :

Illouz, Morgane [Auteur]
Leclercq, Louis-David [Auteur]
Dessenne, Clara [Auteur]
Hatfull, Graham [Auteur]
Daher, Wassim [Auteur]
Kremer, Laurent [Auteur]
Guerardel, Yann [Auteur]
Dessenne, Clara [Auteur]

Journal title :

THE JOURNAL OF BIOLOGICAL CHEMISTRY

Abbreviated title :

J Biol Chem

Pages :

104979

Publication date :

2023-06-28

ISSN :

1083-351X

English keyword(s) :

Mycobacterium abscessus
acetyltransferase
cell wall
glycopeptidolipid
macrophage
mass spectrometry

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Mycobacterium abscessus causes severe lung infections. Clinical isolates can have either smooth (S) or rough (R) colony morphotypes; of these, S but not R variants have abundant cell wall glycopeptidolipids (GPL) consisting ...
Show more >Mycobacterium abscessus causes severe lung infections. Clinical isolates can have either smooth (S) or rough (R) colony morphotypes; of these, S but not R variants have abundant cell wall glycopeptidolipids (GPL) consisting of a peptidolipid core substituted by a 6-deoxy-talose (6-dTal) and rhamnose residues. Deletion of gtf1, encoding the 6-dTal transferase, results in the S-to-R transition, mycobacterial cord formation, and increased virulence, underscoring the importance of 6-dTal in infection outcomes. However, since 6-dTal is di-O-acetylated, it is unclear whether the gtf1 mutant phenotypes are related to the loss of the 6-dTal or the result of the absence of acetylation. Here, we addressed whether M. abscessus atf1 and atf2, encoding two putative O-acetyltransferases located within the gpl biosynthetic locus, transfer acetyl groups to 6-dTal. We found deletion of atf1 and/or atf2 did not drastically alter the GPL acetylation profile, suggesting there are additional enzymes with redundant functions. We subsequently identified two paralogs of atf1 and atf2, MAB_1725c and MAB_3448. While deletion of MAB_1725c and MAB_3448 had no effect on GPL acetylation, the triple atf1-atf2-MAB_1725c mutant did not synthetize fully-acetylated GPL and the quadruple mutant was totally devoid of acetylated GPL. Moreover, both triple and quadruple mutants accumulated hyper-methylated GPL. Finally, we show deletion of atf genes resulted in subtle changes in colony morphology, but had no effect on M. abscessus internalization by macrophages. Overall, these findings reveal the existence of functionally redundant O-acetyltransferases and suggest that O-acetylation influences the glycan moiety of GPL by deflecting biosynthetic flux in M. abscessus.Show less >

Language :

Anglais

Audience :

Non spécifiée

Administrative institution(s) :

Université de Lille
CNRS

Collections :

• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Research team(s) :

Chemical Glycobiology

Submission date :

2023-07-21T12:19:13Z