Open AccessProtein O-mannosylation deficiency increases LprG-associated lipoarabinomannan release by Mycobacterium tuberculosis and enhances the TLR2-associated inflammatory response
Author(s) -
Henar Alonso,
Julien Parra,
Wladimir Malaga,
Delphine Payros,
Chia-Fang Liu,
Céline Berrone,
Camille B. Robert,
Étienne Meunier,
Odile BurletSchiltz,
M. Rivière,
Christophe Guilhot
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08489-7
Subject(s) - lipoarabinomannan , mycobacterium tuberculosis , mycobacterium smegmatis , threonine , mutant , microbiology and biotechnology , secretion , chemistry , tuberculosis , biology , virulence , biochemistry , serine , medicine , enzyme , pathology , gene
Protein O -mannosylation is crucial for the biology of Mycobacterium tuberculosis but the key mannosylated protein(s) involved and its(their) underlying function(s) remain unknown. Here, we demonstrated that the M . tuberculosis mutant (Δ pmt ) deficient for protein O -mannosylation exhibits enhanced release of lipoarabinomannan (LAM) in a complex with LprG, a lipoprotein required for LAM translocation to the cell surface. We determined that LprG is O- mannosylated at a unique threonine position by mass spectrometry analyses of the purified protein. However, although replacement of this amino acid by an alanine residue completely abolished LprG O- mannosylation, the increased release of the LAM/LprG complex was preserved. We found that the increased secretion of this complex is due to enhanced LAM production in the Δ pmt M . tuberculosis and M . smegmatis mutants relative to their wild-type counterparts. This abnormal release of LAM/LprG has functional consequences on the induction of inflammatory responses and provides a possible explanation for the reduced virulence of the M . tuberculosis Δ pmt mutant.