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Biosci Rep. 2018 Dec 18;38(6). pii: BSR20181953. doi: 10.1042/BSR20181953. Print 2018 Dec 21.

LipG a bifunctional phospholipase/thioesterase involved in mycobacterial envelope remodeling.

Author information

1
Aix-Marseille Univ, CNRS, LISM, IMM FR3479, Marseille, France.
2
Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Université de Montpellier, CNRS, ENSCM, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France.
3
Aix-Marseille Univ, CNRS, Centrale Marseille, ISM2, Marseille, France.
4
Department of Chemistry and Biochemistry, University of Missouri, One University Boulevard, St. Louis, MO 63121, U.S.A.
5
Aix-Marseille Univ, CNRS, LISM, IMM FR3479, Marseille, France canaan@imm.cnrs.fr.

Abstract

Tuberculosis caused by Mycobacterium tuberculosis is currently one of the leading causes of death from an infectious agent. The main difficulties encountered in eradicating this bacteria are mainly related to (i) a very complex lipid composition of the bacillus cell wall, (ii) its ability to hide from the immune system inside the granulomas, and (iii) the increasing number of resistant strains. In this context, we were interested in the Rv0646c (lipGMTB ) gene located upstream to the mmaA cluster which is described as being crucial for the production of cell wall components and required for the bacilli adaptation and survival in mouse macrophages. Using biochemical experiments combined with the construction of deletion and overexpression mutant strains in Mycobacterium smegmatis, we found that LipGMTB is a cytoplasmic membrane-associated enzyme that displays both phospholipase and thioesterase activities. Overproduction of LipGMTB decreases the glycopeptidolipids (GPL) level concomitantly to an increase in phosphatidylinositol (PI) which is the precursor of the PI mannoside (PIM), an essential lipid component of the bacterial cell wall. Conversely, deletion of the lipGMS gene in M. smegmatis leads to an overproduction of GPL, and subsequently decreases the strain susceptibility to various antibiotics. All these findings demonstrate that LipG is involved in cell envelope biosynthesis/remodeling, and consequently this enzyme may thus play an important role in mycobacterial physiology.

KEYWORDS:

Mycobacterium tuberculosis; antibiotics; cell-envelope; lipolytic enzymes; phospholipid homeostasis

PMID:
30487163
DOI:
10.1042/BSR20181953

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