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Insights into the smooth‐to‐rough transitioning in Mycobacterium bolletii unravels a functional Tyr residue conserved in all mycobacterial MmpL family members
Author(s) -
Bernut Audrey,
Viljoen Albertus,
Dupont Christian,
Sapriel Guillaume,
Blaise Mickaël,
Bouchier Christiane,
Brosch Roland,
Chastellier Chantal,
Herrmann JeanLouis,
Kremer Laurent
Publication year - 2016
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13283
Subject(s) - biology , virulence , mycobacterium , transmembrane domain , transmembrane protein , genetics , homology (biology) , cell envelope , genome , microbiology and biotechnology , gene , biochemistry , bacteria , escherichia coli , receptor
Summary In mycobacteria, M mp L proteins represent key components that participate in the biosynthesis of the complex cell envelope. Whole genome analysis of a spontaneous rough morphotype variant of M ycobacterium abscessus subsp. bolletii identified a conserved tyrosine that is crucial for the function of M mp L family proteins. Isogenic smooth ( S ) and rough ( R ) variants differed by a single mutation linked to a Y 842 H substitution in M mp L 4a. This mutation caused a deficiency in glycopeptidolipid production/transport in the R variant and a gain in the capacity to produce cords in vitro . I n zebrafish, increased virulence of the M . bolletii R variant over the parental S strain was found, involving massive production of serpentine cords, abscess formation and rapid larval death. Importantly, this finding allowed us to demonstrate an essential role of T yr842 in several different M mp L proteins, including M ycobacterium tuberculosis M mp L 3 . Structural homology models of M mp L 4a and M mp L 3 identified two additional critical residues located in the transmembrane regions TM 10 and TM 4 that are facing each other. We propose that these central residues are part of the proton‐motive force that supplies the energy for substrate transport. Hence, we provide important insights into mechanistic/structural aspects of M mp L proteins as lipid transporters and virulence determinants in mycobacteria.