The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei

Abstract Burkholderia pseudomallei is the causative agent of the tropical disease melioidosis. Its genome encodes an arsenal of virulence factors that allow it, when required, to switch from a soil dwelling bacterium to a deadly intracellular pathogen. With a high intrinsic resistance to antibiotics...

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Autores principales:	Christopher H. Jenkins, Russell Wallis, Natalie Allcock, Kay B. Barnes, Mark I. Richards, Joss M. Auty, Edouard E. Galyov, Sarah V. Harding, Galina V. Mukamolova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8b508a7a185a44429f883627df4c76f9
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spelling	oai:doaj.org-article:8b508a7a185a44429f883627df4c76f92021-12-02T15:08:58ZThe lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei10.1038/s41598-019-47483-z2045-2322https://doaj.org/article/8b508a7a185a44429f883627df4c76f92019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47483-zhttps://doaj.org/toc/2045-2322Abstract Burkholderia pseudomallei is the causative agent of the tropical disease melioidosis. Its genome encodes an arsenal of virulence factors that allow it, when required, to switch from a soil dwelling bacterium to a deadly intracellular pathogen. With a high intrinsic resistance to antibiotics and the ability to overcome challenges from the host immune system, there is an increasing requirement for new antibiotics and a greater understanding into the molecular mechanisms of B. pseudomallei virulence and dormancy. The peptidoglycan remodeling enzymes, lytic transglycosylases (Ltgs) are potential targets for such new antibiotics. Ltgs cleave the glycosidic bonds within bacterial peptidoglycan allowing for the insertion of peptidoglycan precursors during cell growth and division, and cell membrane spanning structures such as flagella and secretion systems. Using bioinformatic analysis we have identified 8 putative Ltgs in B. pseudomallei K96243. We aimed to investigate one of these Ltgs, LtgG (BPSL3046) through the generation of deletion mutants and biochemical analysis. We have shown that LtgG is a key contributor to cellular morphology, division, motility and virulence in BALB/c mice. We have determined the crystal structure of LtgG and have identified various amino acids likely to be important in peptidoglycan binding and catalytic activity. Recombinant protein assays and complementation studies using LtgG containing a site directed mutation in aspartate 343, confirmed the essentiality of this amino acid in the function of LtgG.Christopher H. JenkinsRussell WallisNatalie AllcockKay B. BarnesMark I. RichardsJoss M. AutyEdouard E. GalyovSarah V. HardingGalina V. MukamolovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christopher H. Jenkins Russell Wallis Natalie Allcock Kay B. Barnes Mark I. Richards Joss M. Auty Edouard E. Galyov Sarah V. Harding Galina V. Mukamolova The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei
description	Abstract Burkholderia pseudomallei is the causative agent of the tropical disease melioidosis. Its genome encodes an arsenal of virulence factors that allow it, when required, to switch from a soil dwelling bacterium to a deadly intracellular pathogen. With a high intrinsic resistance to antibiotics and the ability to overcome challenges from the host immune system, there is an increasing requirement for new antibiotics and a greater understanding into the molecular mechanisms of B. pseudomallei virulence and dormancy. The peptidoglycan remodeling enzymes, lytic transglycosylases (Ltgs) are potential targets for such new antibiotics. Ltgs cleave the glycosidic bonds within bacterial peptidoglycan allowing for the insertion of peptidoglycan precursors during cell growth and division, and cell membrane spanning structures such as flagella and secretion systems. Using bioinformatic analysis we have identified 8 putative Ltgs in B. pseudomallei K96243. We aimed to investigate one of these Ltgs, LtgG (BPSL3046) through the generation of deletion mutants and biochemical analysis. We have shown that LtgG is a key contributor to cellular morphology, division, motility and virulence in BALB/c mice. We have determined the crystal structure of LtgG and have identified various amino acids likely to be important in peptidoglycan binding and catalytic activity. Recombinant protein assays and complementation studies using LtgG containing a site directed mutation in aspartate 343, confirmed the essentiality of this amino acid in the function of LtgG.
format	article
author	Christopher H. Jenkins Russell Wallis Natalie Allcock Kay B. Barnes Mark I. Richards Joss M. Auty Edouard E. Galyov Sarah V. Harding Galina V. Mukamolova
author_facet	Christopher H. Jenkins Russell Wallis Natalie Allcock Kay B. Barnes Mark I. Richards Joss M. Auty Edouard E. Galyov Sarah V. Harding Galina V. Mukamolova
author_sort	Christopher H. Jenkins
title	The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei
title_short	The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei
title_full	The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei
title_fullStr	The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei
title_full_unstemmed	The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei
title_sort	lytic transglycosylase, ltgg, controls cell morphology and virulence in burkholderia pseudomallei
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/8b508a7a185a44429f883627df4c76f9
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The lytic transglycosylase, LtgG, controls cell morphology and virulence in Burkholderia pseudomallei

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