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Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis

Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has a unique cell envelope which accounts for its unusual low permeability and contributes to resistance against common antibiotics. The main structural elements of the cell wall consist of a cross-linked network of peptidoglyca...

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Autores principales: Harrison, James, Lloyd, Georgina, Joe, Maju, Lowary, Todd L., Reynolds, Edward, Walters-Morgan, Hannah, Bhatt, Apoorva, Lovering, Andrew, Besra, Gurdyal S., Alderwick, Luke J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981717/
https://www.ncbi.nlm.nih.gov/pubmed/27486192
http://dx.doi.org/10.1128/mBio.00972-16
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author Harrison, James
Lloyd, Georgina
Joe, Maju
Lowary, Todd L.
Reynolds, Edward
Walters-Morgan, Hannah
Bhatt, Apoorva
Lovering, Andrew
Besra, Gurdyal S.
Alderwick, Luke J.
author_facet Harrison, James
Lloyd, Georgina
Joe, Maju
Lowary, Todd L.
Reynolds, Edward
Walters-Morgan, Hannah
Bhatt, Apoorva
Lovering, Andrew
Besra, Gurdyal S.
Alderwick, Luke J.
author_sort Harrison, James
collection PubMed
description Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has a unique cell envelope which accounts for its unusual low permeability and contributes to resistance against common antibiotics. The main structural elements of the cell wall consist of a cross-linked network of peptidoglycan (PG) in which some of the muramic acid residues are covalently attached to a complex polysaccharide, arabinogalactan (AG), via a unique α-l-rhamnopyranose–(1→3)-α-d-GlcNAc-(1→P) linker unit. While the molecular genetics associated with PG and AG biosynthetic pathways have been largely delineated, the mechanism by which these two major pathways converge has remained elusive. In Gram-positive organisms, the LytR-CpsA-Psr (LCP) family of proteins are responsible for ligating cell wall teichoic acids to peptidoglycan, through a linker unit that bears a striking resemblance to that found in mycobacterial arabinogalactan. In this study, we have identified Rv3267 as a mycobacterial LCP homolog gene that encodes a phosphotransferase which we have named Lcp1. We demonstrate that lcp1 is an essential gene required for cell viability and show that recombinant Lcp1 is capable of ligating AG to PG in a cell-free radiolabeling assay.
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spelling pubmed-49817172016-08-17 Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis Harrison, James Lloyd, Georgina Joe, Maju Lowary, Todd L. Reynolds, Edward Walters-Morgan, Hannah Bhatt, Apoorva Lovering, Andrew Besra, Gurdyal S. Alderwick, Luke J. mBio Research Article Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has a unique cell envelope which accounts for its unusual low permeability and contributes to resistance against common antibiotics. The main structural elements of the cell wall consist of a cross-linked network of peptidoglycan (PG) in which some of the muramic acid residues are covalently attached to a complex polysaccharide, arabinogalactan (AG), via a unique α-l-rhamnopyranose–(1→3)-α-d-GlcNAc-(1→P) linker unit. While the molecular genetics associated with PG and AG biosynthetic pathways have been largely delineated, the mechanism by which these two major pathways converge has remained elusive. In Gram-positive organisms, the LytR-CpsA-Psr (LCP) family of proteins are responsible for ligating cell wall teichoic acids to peptidoglycan, through a linker unit that bears a striking resemblance to that found in mycobacterial arabinogalactan. In this study, we have identified Rv3267 as a mycobacterial LCP homolog gene that encodes a phosphotransferase which we have named Lcp1. We demonstrate that lcp1 is an essential gene required for cell viability and show that recombinant Lcp1 is capable of ligating AG to PG in a cell-free radiolabeling assay. American Society for Microbiology 2016-08-02 /pmc/articles/PMC4981717/ /pubmed/27486192 http://dx.doi.org/10.1128/mBio.00972-16 Text en Copyright © 2016 Harrison et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Harrison, James
Lloyd, Georgina
Joe, Maju
Lowary, Todd L.
Reynolds, Edward
Walters-Morgan, Hannah
Bhatt, Apoorva
Lovering, Andrew
Besra, Gurdyal S.
Alderwick, Luke J.
Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis
title Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis
title_full Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis
title_fullStr Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis
title_full_unstemmed Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis
title_short Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in Mycobacterium tuberculosis
title_sort lcp1 is a phosphotransferase responsible for ligating arabinogalactan to peptidoglycan in mycobacterium tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981717/
https://www.ncbi.nlm.nih.gov/pubmed/27486192
http://dx.doi.org/10.1128/mBio.00972-16
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