Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin

Abstract Secretion of pertussis toxin (PT) is the preeminent virulence trait of the human pathogen Bordetella pertussis, causing whooping cough. Bordetella bronchiseptica, although it harbors an intact 12-kb ptx–ptl operon, does not express PT due to an inactive ptx promoter (Pptx), which contains 1...

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Autores principales:	Qing Chen, Mary C. Gray, Erik Hewlett, Scott Stibitz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/47688debb2dd416288a3a86026def9cd
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spelling	oai:doaj.org-article:47688debb2dd416288a3a86026def9cd2021-12-02T17:16:17ZFour single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin10.1038/s41598-021-88852-x2045-2322https://doaj.org/article/47688debb2dd416288a3a86026def9cd2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88852-xhttps://doaj.org/toc/2045-2322Abstract Secretion of pertussis toxin (PT) is the preeminent virulence trait of the human pathogen Bordetella pertussis, causing whooping cough. Bordetella bronchiseptica, although it harbors an intact 12-kb ptx–ptl operon, does not express PT due to an inactive ptx promoter (Pptx), which contains 18 SNPs (single nucleotide polymorphisms) relative to B. pertussis Pptx. A systematic analysis of these SNPs was undertaken to define the degree of mutational divergence necessary to activate B. bronchiseptica Pptx. A single change (C−13T), which created a better − 10 element, was capable of activating B. bronchiseptica Pptx sufficiently to allow secretion of low but measureable levels of active PT. Three additional changes in the BvgA-binding region, only in the context of C−13T mutant, raised the expression of PT to B. pertussis levels. These results illuminate a logical evolutionary pathway for acquisition of this key virulence trait in the evolution of B. pertussis from a B. bronchiseptica-like common ancestor.Qing ChenMary C. GrayErik HewlettScott StibitzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qing Chen Mary C. Gray Erik Hewlett Scott Stibitz Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
description	Abstract Secretion of pertussis toxin (PT) is the preeminent virulence trait of the human pathogen Bordetella pertussis, causing whooping cough. Bordetella bronchiseptica, although it harbors an intact 12-kb ptx–ptl operon, does not express PT due to an inactive ptx promoter (Pptx), which contains 18 SNPs (single nucleotide polymorphisms) relative to B. pertussis Pptx. A systematic analysis of these SNPs was undertaken to define the degree of mutational divergence necessary to activate B. bronchiseptica Pptx. A single change (C−13T), which created a better − 10 element, was capable of activating B. bronchiseptica Pptx sufficiently to allow secretion of low but measureable levels of active PT. Three additional changes in the BvgA-binding region, only in the context of C−13T mutant, raised the expression of PT to B. pertussis levels. These results illuminate a logical evolutionary pathway for acquisition of this key virulence trait in the evolution of B. pertussis from a B. bronchiseptica-like common ancestor.
format	article
author	Qing Chen Mary C. Gray Erik Hewlett Scott Stibitz
author_facet	Qing Chen Mary C. Gray Erik Hewlett Scott Stibitz
author_sort	Qing Chen
title	Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
title_short	Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
title_full	Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
title_fullStr	Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
title_full_unstemmed	Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
title_sort	four single-basepair mutations in the ptx promoter of bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/47688debb2dd416288a3a86026def9cd
work_keys_str_mv	AT qingchen foursinglebasepairmutationsintheptxpromoterofbordetellabronchisepticaaresufficienttoactivatetheexpressionofpertussistoxin AT marycgray foursinglebasepairmutationsintheptxpromoterofbordetellabronchisepticaaresufficienttoactivatetheexpressionofpertussistoxin AT erikhewlett foursinglebasepairmutationsintheptxpromoterofbordetellabronchisepticaaresufficienttoactivatetheexpressionofpertussistoxin AT scottstibitz foursinglebasepairmutationsintheptxpromoterofbordetellabronchisepticaaresufficienttoactivatetheexpressionofpertussistoxin
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Four single-basepair mutations in the ptx promoter of Bordetella bronchiseptica are sufficient to activate the expression of pertussis toxin

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