The ppm operon is essential for acylation and glycosylation of lipoproteins in Corynebacterium glutamicum

Due to their contribution to bacterial virulence, lipoproteins and members of the lipoprotein biogenesis pathway represent potent drug targets. Following translocation across the inner membrane, lipoprotein precursors are acylated by lipoprotein diacylglycerol transferase (Lgt), cleaved off their si...

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Bibliographic Details
Published in:PloS one 2012-09, Vol.7 (9), p.e46225
Main Authors: Mohiman, Niloofar, Argentini, Manuela, Batt, Sarah M, Cornu, David, Masi, Muriel, Eggeling, Lothar, Besra, Gurdyal, Bayan, Nicolas
Format: Article
Language:English
Subjects:
Acylation
Acyltransferase
Acyltransferases - genetics
Acyltransferases - metabolism
Amino Acid Sequence
Antigens
Apolipoproteins
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Besra
Biology
Biosynthesis
Cell division
Chemical Sciences
Chromatography, Liquid
Corynebacteria
Corynebacterium glutamicum
Corynebacterium glutamicum - enzymology
Corynebacterium glutamicum - genetics
Diacylglycerol
Diglycerides
E coli
Escherichia coli
Escherichia coli - genetics
Gene Expression
Genetic aspects
Glycosylation
Gram-negative bacteria
Gram-positive bacteria
Hexose
Homology
Isoenzymes - genetics
Isoenzymes - metabolism
Lipoproteins
Lipoproteins - genetics
Lipoproteins - metabolism
Molecular Sequence Data
Mutants
Mutation
Mycobacterium
Mycobacterium tuberculosis
Mycobacterium tuberculosis - enzymology
Mycobacterium tuberculosis - genetics
Operon
Organic chemistry
Peptides
Physiological aspects
Post-translation
Protein Processing, Post-Translational
Proteins
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Signal peptidase
Signal peptides
Spectrometry, Mass, Electrospray Ionization
Streptomyces
Translocation
Tuberculosis
Virulence
Virulence (Microbiology)
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Summary:Due to their contribution to bacterial virulence, lipoproteins and members of the lipoprotein biogenesis pathway represent potent drug targets. Following translocation across the inner membrane, lipoprotein precursors are acylated by lipoprotein diacylglycerol transferase (Lgt), cleaved off their signal peptides by lipoprotein signal peptidase (Lsp) and, in Gram-negative bacteria, further triacylated by lipoprotein N-acyl transferase (Lnt). The existence of an active apolipoprotein N-acyltransferase (Ms-Ppm2) involved in the N-acylation of LppX was recently reported in M. smegmatis. Ms-Ppm2 is part of the ppm operon in which Ppm1, a polyprenol-monophosphomannose synthase, has been shown to be essential in lipoglycans synthesis but whose function in lipoprotein biosynthesis is completely unknown. In order to clarify the role of the ppm operon in lipoprotein biosynthesis, we investigated the post-translational modifications of two model lipoproteins (AmyE and LppX) in C. glutamicum Δppm1 and Δppm2 mutants. Our results show that both proteins are anchored into the membrane and that their N-termini are N-acylated by Cg-Ppm2. The acylated N-terminal peptide of LppX was also found to be modified by hexose moieties. This O-glycosylation is localized in the N-terminal peptide of LppX and disappeared in the Δppm1 mutant. While compromised in the absence of Cg-Ppm2, LppX O-glycosylation could be restored when Cg-Ppm1, Cg-Ppm2 or the homologous Mt-Ppm1 of M. tuberculosis was overexpressed. Together, these results show for the first time that Cg-Ppm1 (Ppm synthase) and Cg-Ppm2 (Lnt) operate in a common biosynthetic pathway in which lipoprotein N-acylation and glycosylation are tightly coupled.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0046225