Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>

ABSTRACT 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 pep...

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Autores principales:	James Harrison, Georgina Lloyd, Maju Joe, Todd L. Lowary, Edward Reynolds, Hannah Walters-Morgan, Apoorva Bhatt, Andrew Lovering, Gurdyal S. Besra, Luke J. Alderwick
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a3223e2e64154308893256d5b2e5c943
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spelling	oai:doaj.org-article:a3223e2e64154308893256d5b2e5c9432021-11-15T15:50:18ZLcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>10.1128/mBio.00972-162150-7511https://doaj.org/article/a3223e2e64154308893256d5b2e5c9432016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00972-16https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Tuberculosis is an infectious disease caused by the bacterial organism Mycobacterium tuberculosis. Survival of M. tuberculosis rests critically on the integrity of its unique cell wall; therefore, a better understanding of how the genes and enzymes involved in cell wall assembly work is fundamental for us to develop new drugs to treat this disease. In this study, we have identified Lcp1 as an essential phosphotransferase that ligates together arabinogalactan and peptidoglycan, two crucial cell wall macromolecules found within the mycobacterial cell wall. The discovery of Lcp1 sheds new light on the final stages of mycobacterial cell wall assembly and represents a key biosynthetic step that could be exploited for new anti-TB drug discovery.James HarrisonGeorgina LloydMaju JoeTodd L. LowaryEdward ReynoldsHannah Walters-MorganApoorva BhattAndrew LoveringGurdyal S. BesraLuke J. AlderwickAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 James Harrison Georgina Lloyd Maju Joe Todd L. Lowary Edward Reynolds Hannah Walters-Morgan Apoorva Bhatt Andrew Lovering Gurdyal S. Besra Luke J. Alderwick Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
description	ABSTRACT 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. IMPORTANCE Tuberculosis is an infectious disease caused by the bacterial organism Mycobacterium tuberculosis. Survival of M. tuberculosis rests critically on the integrity of its unique cell wall; therefore, a better understanding of how the genes and enzymes involved in cell wall assembly work is fundamental for us to develop new drugs to treat this disease. In this study, we have identified Lcp1 as an essential phosphotransferase that ligates together arabinogalactan and peptidoglycan, two crucial cell wall macromolecules found within the mycobacterial cell wall. The discovery of Lcp1 sheds new light on the final stages of mycobacterial cell wall assembly and represents a key biosynthetic step that could be exploited for new anti-TB drug discovery.
format	article
author	James Harrison Georgina Lloyd Maju Joe Todd L. Lowary Edward Reynolds Hannah Walters-Morgan Apoorva Bhatt Andrew Lovering Gurdyal S. Besra Luke J. Alderwick
author_facet	James Harrison Georgina Lloyd Maju Joe Todd L. Lowary Edward Reynolds Hannah Walters-Morgan Apoorva Bhatt Andrew Lovering Gurdyal S. Besra Luke J. Alderwick
author_sort	James Harrison
title	Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
title_short	Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
title_full	Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
title_fullStr	Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
title_full_unstemmed	Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>
title_sort	lcp1 is a phosphotransferase responsible for ligating arabinogalactan to peptidoglycan in <named-content content-type="genus-species">mycobacterium tuberculosis</named-content>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/a3223e2e64154308893256d5b2e5c943
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Lcp1 Is a Phosphotransferase Responsible for Ligating Arabinogalactan to Peptidoglycan in <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content>

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