PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans

Streptococcus mutans , a cariogenic species, is often associated with cardiovascular infections. Systemic virulence of specific S. mutans serotypes has been associated with the expression of the collagen- and laminin-binding protein Cnm, which is transcriptionally regulated by VicRK and CovR. In thi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lívia A. Alves, Tridib Ganguly, Érika N. Harth-Chú, Jessica Kajfasz, José A. Lemos, Jacqueline Abranches, Renata O. Mattos-Graner
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	streptococcus mutans systemic infections two component system peptidases complement system cardiovascular diseases Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/bb8627b2fce041bba7c539bcd97e3089
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bb8627b2fce041bba7c539bcd97e3089
record_format	dspace
spelling	oai:doaj.org-article:bb8627b2fce041bba7c539bcd97e30892021-11-17T14:21:58ZPepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans2150-55942150-560810.1080/21505594.2020.1767377https://doaj.org/article/bb8627b2fce041bba7c539bcd97e30892020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1767377https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Streptococcus mutans , a cariogenic species, is often associated with cardiovascular infections. Systemic virulence of specific S. mutans serotypes has been associated with the expression of the collagen- and laminin-binding protein Cnm, which is transcriptionally regulated by VicRK and CovR. In this study, we characterized a VicRK- and CovR-regulated gene, pepO, coding for a conserved endopeptidase. Transcriptional and protein analyses revealed that pepO is highly expressed in S. mutans strains resistant to complement immunity (blood isolates) compared to oral isolates. Gel mobility assay, transcriptional, and Western blot analyses revealed that pepO is repressed by VicR and induced by CovR. Deletion of pepO in the Cnm+ strain OMZ175 (OMZpepO) or in the Cnm− UA159 (UApepO) led to an increased susceptibility to C3b deposition, and to low binding to complement proteins C1q and C4BP. Additionally, pepO mutants showed diminished ex vivo survival in human blood and impaired capacity to kill G. mellonella larvae. Inactivation of cnm in OMZ175 (OMZcnm) resulted in increased resistance to C3b deposition and unaltered blood survival, although both pepO and cnm mutants displayed attenuated virulence in G. mellonella. Unlike OMZcnm, OMZpepO could invade HCAEC endothelial cells. Supporting these phenotypes, recombinant proteins rPepO and rCnmA showed specific profiles of binding to C1q, C4BP, and to other plasma (plasminogen, fibronectin) and extracellular matrix proteins (type I collagen, laminin). Therefore this study identifies a novel VicRK/CovR-target required for immune evasion and host persistence, pepO, expanding the roles of VicRK and CovR in regulating S. mutans virulence.Lívia A. AlvesTridib GangulyÉrika N. Harth-ChúJessica KajfaszJosé A. LemosJacqueline AbranchesRenata O. Mattos-GranerTaylor & Francis Grouparticlestreptococcus mutanssystemic infectionstwo component systempeptidasescomplement systemcardiovascular diseasesInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 521-536 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	streptococcus mutans systemic infections two component system peptidases complement system cardiovascular diseases Infectious and parasitic diseases RC109-216
spellingShingle	streptococcus mutans systemic infections two component system peptidases complement system cardiovascular diseases Infectious and parasitic diseases RC109-216 Lívia A. Alves Tridib Ganguly Érika N. Harth-Chú Jessica Kajfasz José A. Lemos Jacqueline Abranches Renata O. Mattos-Graner PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans
description	Streptococcus mutans , a cariogenic species, is often associated with cardiovascular infections. Systemic virulence of specific S. mutans serotypes has been associated with the expression of the collagen- and laminin-binding protein Cnm, which is transcriptionally regulated by VicRK and CovR. In this study, we characterized a VicRK- and CovR-regulated gene, pepO, coding for a conserved endopeptidase. Transcriptional and protein analyses revealed that pepO is highly expressed in S. mutans strains resistant to complement immunity (blood isolates) compared to oral isolates. Gel mobility assay, transcriptional, and Western blot analyses revealed that pepO is repressed by VicR and induced by CovR. Deletion of pepO in the Cnm+ strain OMZ175 (OMZpepO) or in the Cnm− UA159 (UApepO) led to an increased susceptibility to C3b deposition, and to low binding to complement proteins C1q and C4BP. Additionally, pepO mutants showed diminished ex vivo survival in human blood and impaired capacity to kill G. mellonella larvae. Inactivation of cnm in OMZ175 (OMZcnm) resulted in increased resistance to C3b deposition and unaltered blood survival, although both pepO and cnm mutants displayed attenuated virulence in G. mellonella. Unlike OMZcnm, OMZpepO could invade HCAEC endothelial cells. Supporting these phenotypes, recombinant proteins rPepO and rCnmA showed specific profiles of binding to C1q, C4BP, and to other plasma (plasminogen, fibronectin) and extracellular matrix proteins (type I collagen, laminin). Therefore this study identifies a novel VicRK/CovR-target required for immune evasion and host persistence, pepO, expanding the roles of VicRK and CovR in regulating S. mutans virulence.
format	article
author	Lívia A. Alves Tridib Ganguly Érika N. Harth-Chú Jessica Kajfasz José A. Lemos Jacqueline Abranches Renata O. Mattos-Graner
author_facet	Lívia A. Alves Tridib Ganguly Érika N. Harth-Chú Jessica Kajfasz José A. Lemos Jacqueline Abranches Renata O. Mattos-Graner
author_sort	Lívia A. Alves
title	PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans
title_short	PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans
title_full	PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans
title_fullStr	PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans
title_full_unstemmed	PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans
title_sort	pepo is a target of the two-component systems vicrk and covr required for systemic virulence of streptococcus mutans
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/bb8627b2fce041bba7c539bcd97e3089
work_keys_str_mv	AT liviaaalves pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans AT tridibganguly pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans AT erikanharthchu pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans AT jessicakajfasz pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans AT josealemos pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans AT jacquelineabranches pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans AT renataomattosgraner pepoisatargetofthetwocomponentsystemsvicrkandcovrrequiredforsystemicvirulenceofstreptococcusmutans
_version_	1718425505748746240

PepO is a target of the two-component systems VicRK and CovR required for systemic virulence of Streptococcus mutans

Ejemplares similares