HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate

ABSTRACT Borrelia burgdorferi HtrA (HtrABb) is a serine protease that targets damaged or improperly folded proteins. In our previous studies, HtrABb specifically degraded basic membrane protein BmpD, chemotaxis phosphatase CheX, and outer membrane protein P66. In addition, HtrABb degrades virulence...

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Autores principales:	James L. Coleman, Alvaro Toledo, Jorge L. Benach
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Borrelia glycolytic enzymes HtrA P66 swarm motility Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/93f59c4552e2413ba6af9493bfeeda29
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spelling	oai:doaj.org-article:93f59c4552e2413ba6af9493bfeeda292021-11-15T16:00:15ZHtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate10.1128/mBio.01136-182150-7511https://doaj.org/article/93f59c4552e2413ba6af9493bfeeda292018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01136-18https://doaj.org/toc/2150-7511ABSTRACT Borrelia burgdorferi HtrA (HtrABb) is a serine protease that targets damaged or improperly folded proteins. In our previous studies, HtrABb specifically degraded basic membrane protein BmpD, chemotaxis phosphatase CheX, and outer membrane protein P66. In addition, HtrABb degrades virulence factor BB0323 and components of the extracellular matrix fibronectin and aggrecan. A proteomics-based analysis (two-dimensional difference gel electrophoresis [2-D DIGE], liquid chromatography-mass spectrometry [LC-MS]) of an HtrABb-overexpressing strain of B. burgdorferi (A3HtrAOE) revealed that protein levels of P66 were reduced in comparison to wild-type B. burgdorferi, confirming its status as an HtrABb substrate. Hbb, a P66-DNA-binding transcription factor, was specifically degraded by HtrABb, providing supportive evidence for a role for both in the regulation of P66. A3HtrAOE exhibited reduced motility in swarm assays, a possible link between overabundance of HtrABb and its enzymatic specificity for P66. However, the ΔP66 strain did not have reduced motility in the swarm assays, negating a role for this protein. The proteomics analyses also identified three enzymes of the glycolytic pathway, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerol-3-phosphate dehydrogenase (GPDH), and glycerol kinase (GK), and one enzyme involved in carbohydrate metabolism, diphosphate-fructose-6-phosphate 1-phosphotransferase, which were reduced in A3HtrAOE. Consistent with its reduced protein levels of these glycolytic enzymes, A3HtrAOE was also deficient in production of pyruvate. We propose a model for a role for HtrABb in contributing to a decrease in metabolic activity of B. burgdorferi. IMPORTANCE Being a vector-borne bacterium, B. burgdorferi must remodel its protein content as it transfers from tick to mammal. Proteolysis is a mechanism whereby remodeling can be accomplished. HtrABb degrades a number of proteins whose disappearance may help in preparing this organism for a stage of low metabolic activity.James L. ColemanAlvaro ToledoJorge L. BenachAmerican Society for MicrobiologyarticleBorreliaglycolytic enzymesHtrAP66swarm motilityMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Borrelia glycolytic enzymes HtrA P66 swarm motility Microbiology QR1-502
spellingShingle	Borrelia glycolytic enzymes HtrA P66 swarm motility Microbiology QR1-502 James L. Coleman Alvaro Toledo Jorge L. Benach HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
description	ABSTRACT Borrelia burgdorferi HtrA (HtrABb) is a serine protease that targets damaged or improperly folded proteins. In our previous studies, HtrABb specifically degraded basic membrane protein BmpD, chemotaxis phosphatase CheX, and outer membrane protein P66. In addition, HtrABb degrades virulence factor BB0323 and components of the extracellular matrix fibronectin and aggrecan. A proteomics-based analysis (two-dimensional difference gel electrophoresis [2-D DIGE], liquid chromatography-mass spectrometry [LC-MS]) of an HtrABb-overexpressing strain of B. burgdorferi (A3HtrAOE) revealed that protein levels of P66 were reduced in comparison to wild-type B. burgdorferi, confirming its status as an HtrABb substrate. Hbb, a P66-DNA-binding transcription factor, was specifically degraded by HtrABb, providing supportive evidence for a role for both in the regulation of P66. A3HtrAOE exhibited reduced motility in swarm assays, a possible link between overabundance of HtrABb and its enzymatic specificity for P66. However, the ΔP66 strain did not have reduced motility in the swarm assays, negating a role for this protein. The proteomics analyses also identified three enzymes of the glycolytic pathway, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerol-3-phosphate dehydrogenase (GPDH), and glycerol kinase (GK), and one enzyme involved in carbohydrate metabolism, diphosphate-fructose-6-phosphate 1-phosphotransferase, which were reduced in A3HtrAOE. Consistent with its reduced protein levels of these glycolytic enzymes, A3HtrAOE was also deficient in production of pyruvate. We propose a model for a role for HtrABb in contributing to a decrease in metabolic activity of B. burgdorferi. IMPORTANCE Being a vector-borne bacterium, B. burgdorferi must remodel its protein content as it transfers from tick to mammal. Proteolysis is a mechanism whereby remodeling can be accomplished. HtrABb degrades a number of proteins whose disappearance may help in preparing this organism for a stage of low metabolic activity.
format	article
author	James L. Coleman Alvaro Toledo Jorge L. Benach
author_facet	James L. Coleman Alvaro Toledo Jorge L. Benach
author_sort	James L. Coleman
title	HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
title_short	HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
title_full	HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
title_fullStr	HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
title_full_unstemmed	HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
title_sort	htra of <named-content content-type="genus-species">borrelia burgdorferi</named-content> leads to decreased swarm motility and decreased production of pyruvate
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/93f59c4552e2413ba6af9493bfeeda29
work_keys_str_mv	AT jameslcoleman htraofnamedcontentcontenttypegenusspeciesborreliaburgdorferinamedcontentleadstodecreasedswarmmotilityanddecreasedproductionofpyruvate AT alvarotoledo htraofnamedcontentcontenttypegenusspeciesborreliaburgdorferinamedcontentleadstodecreasedswarmmotilityanddecreasedproductionofpyruvate AT jorgelbenach htraofnamedcontentcontenttypegenusspeciesborreliaburgdorferinamedcontentleadstodecreasedswarmmotilityanddecreasedproductionofpyruvate
_version_	1718426982960594944

HtrA of <named-content content-type="genus-species">Borrelia burgdorferi</named-content> Leads to Decreased Swarm Motility and Decreased Production of Pyruvate

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