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Lipoprotein Glycosylation by Protein-O-Mannosyltransferase (MAB_1122c) Contributes to Low Cell Envelope Permeability and Antibiotic Resistance of Mycobacterium abscessus


Becker, Katja; Haldimann, Klara; Selchow, Petra; Reinau, Lukas M; Dal Molin, Michael; Sander, Peter (2017). Lipoprotein Glycosylation by Protein-O-Mannosyltransferase (MAB_1122c) Contributes to Low Cell Envelope Permeability and Antibiotic Resistance of Mycobacterium abscessus. Frontiers in Microbiology, 8:2123.

Abstract

Lipoproteins are important components of the mycobacterial cell envelope due to their function in cell wall homeostasis and bacterial virulence. They are post-translationally modified with lipid- and glycosyl-residues in various species and interference with acylation or glycosylation leads to reduced growth and attenuated virulence in Mycobacterium tuberculosis. Lipoproteins are also expressed in the emerging and highly drug resistant pathogen Mycobacterium abscessus which frequently affects the lungs of patients with chronic pulmonary disease or cystic fibrosis. We investigated post-translational modification, acylation and glycosylation, of heterologously expressed (M. tuberculosis LppX and Mpt83) and endogenous (SodC) lipoproteins at the molecular level in M. abscessus and identified MAB_1122c as protein O-mannosyltransferase (Pmt). Both, heterologous and endogenous lipoproteins carried a characteristic lipid anchor with palmitic acid (C16), palmitoleic acid (C16:1), oleic acid (C18), or tuberculostearic acid (C19) modifications. Multiple hexose-moieties were detected in the N-terminal region of the model lipoproteins expressed in M. abscessus. Conservation of lipoprotein glycosylation in M. tuberculosis and M. abscessus was revealed and points toward the existence of an O-glycosylation motif or other regulatory mechanisms regarding this post-translational modification. Deletion of MAB_1122c prevented glycosylation and affected susceptibility to specific antibiotics which are large or target peptidoglycan synthesis and to lysozyme. Cell envelope permeability of M. abscessus Δpmt was increased and mutant bacteria showed reduced survival inside macrophages. The results provide a link between post-translational modification of lipoproteins and the permeability of the mycobacterial cell envelope which stresses the importance of lipoproteins as components of this complex structure.

Abstract

Lipoproteins are important components of the mycobacterial cell envelope due to their function in cell wall homeostasis and bacterial virulence. They are post-translationally modified with lipid- and glycosyl-residues in various species and interference with acylation or glycosylation leads to reduced growth and attenuated virulence in Mycobacterium tuberculosis. Lipoproteins are also expressed in the emerging and highly drug resistant pathogen Mycobacterium abscessus which frequently affects the lungs of patients with chronic pulmonary disease or cystic fibrosis. We investigated post-translational modification, acylation and glycosylation, of heterologously expressed (M. tuberculosis LppX and Mpt83) and endogenous (SodC) lipoproteins at the molecular level in M. abscessus and identified MAB_1122c as protein O-mannosyltransferase (Pmt). Both, heterologous and endogenous lipoproteins carried a characteristic lipid anchor with palmitic acid (C16), palmitoleic acid (C16:1), oleic acid (C18), or tuberculostearic acid (C19) modifications. Multiple hexose-moieties were detected in the N-terminal region of the model lipoproteins expressed in M. abscessus. Conservation of lipoprotein glycosylation in M. tuberculosis and M. abscessus was revealed and points toward the existence of an O-glycosylation motif or other regulatory mechanisms regarding this post-translational modification. Deletion of MAB_1122c prevented glycosylation and affected susceptibility to specific antibiotics which are large or target peptidoglycan synthesis and to lysozyme. Cell envelope permeability of M. abscessus Δpmt was increased and mutant bacteria showed reduced survival inside macrophages. The results provide a link between post-translational modification of lipoproteins and the permeability of the mycobacterial cell envelope which stresses the importance of lipoproteins as components of this complex structure.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Functional Genomics Center Zurich
04 Faculty of Medicine > Institute of Medical Microbiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2017
Deposited On:26 Jan 2018 12:39
Last Modified:19 Feb 2018 10:35
Publisher:Frontiers Research Foundation
ISSN:1664-302X
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3389/fmicb.2017.02123
PubMed ID:29163413

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