Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.

Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the history of tuberculosis research are Mycobac...

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Autores principales:	Wafa Frigui, Daria Bottai, Laleh Majlessi, Marc Monot, Emmanuelle Josselin, Priscille Brodin, Thierry Garnier, Brigitte Gicquel, Carlos Martin, Claude Leclerc, Stewart T Cole, Roland Brosch
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b6751aedc31a4e9cbe618a67b8fd11cd
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spelling	oai:doaj.org-article:b6751aedc31a4e9cbe618a67b8fd11cd2021-11-25T05:46:43ZControl of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.1553-73661553-737410.1371/journal.ppat.0040033https://doaj.org/article/b6751aedc31a4e9cbe618a67b8fd11cd2008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18282096/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the history of tuberculosis research are Mycobacterium bovis BCG (BCG) and Mycobacterium tuberculosis H37Ra (H37Ra), which both lost their virulence during in vitro serial passage. Whereas the attenuation of BCG is due mainly to loss of the ESAT-6 secretion system, ESX-1, the reason why H37Ra is attenuated remained unknown. However, here we show that a point mutation (S219L) in the predicted DNA binding region of the regulator PhoP is involved in the attenuation of H37Ra via a mechanism that impacts on the secretion of the major T cell antigen ESAT-6. Only H37Ra "knock-ins" that carried an integrated cosmid with the wild-type phoP gene from M. tuberculosis H37Rv showed changes in colony morphology, increased virulence, ESAT-6 secretion, and induction of specific T cell responses, whereas other H37Ra constructs did not. This finding established a link between the PhoP regulator and ESAT-6 secretion that opens exciting new perspectives for elucidating virulence regulation in M. tuberculosis.Wafa FriguiDaria BottaiLaleh MajlessiMarc MonotEmmanuelle JosselinPriscille BrodinThierry GarnierBrigitte GicquelCarlos MartinClaude LeclercStewart T ColeRoland BroschPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 2, p e33 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Wafa Frigui Daria Bottai Laleh Majlessi Marc Monot Emmanuelle Josselin Priscille Brodin Thierry Garnier Brigitte Gicquel Carlos Martin Claude Leclerc Stewart T Cole Roland Brosch Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.
description	Analysis of mycobacterial strains that have lost their ability to cause disease is a powerful approach to identify yet unknown virulence determinants and pathways involved in tuberculosis pathogenesis. Two of the most widely used attenuated strains in the history of tuberculosis research are Mycobacterium bovis BCG (BCG) and Mycobacterium tuberculosis H37Ra (H37Ra), which both lost their virulence during in vitro serial passage. Whereas the attenuation of BCG is due mainly to loss of the ESAT-6 secretion system, ESX-1, the reason why H37Ra is attenuated remained unknown. However, here we show that a point mutation (S219L) in the predicted DNA binding region of the regulator PhoP is involved in the attenuation of H37Ra via a mechanism that impacts on the secretion of the major T cell antigen ESAT-6. Only H37Ra "knock-ins" that carried an integrated cosmid with the wild-type phoP gene from M. tuberculosis H37Rv showed changes in colony morphology, increased virulence, ESAT-6 secretion, and induction of specific T cell responses, whereas other H37Ra constructs did not. This finding established a link between the PhoP regulator and ESAT-6 secretion that opens exciting new perspectives for elucidating virulence regulation in M. tuberculosis.
format	article
author	Wafa Frigui Daria Bottai Laleh Majlessi Marc Monot Emmanuelle Josselin Priscille Brodin Thierry Garnier Brigitte Gicquel Carlos Martin Claude Leclerc Stewart T Cole Roland Brosch
author_facet	Wafa Frigui Daria Bottai Laleh Majlessi Marc Monot Emmanuelle Josselin Priscille Brodin Thierry Garnier Brigitte Gicquel Carlos Martin Claude Leclerc Stewart T Cole Roland Brosch
author_sort	Wafa Frigui
title	Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.
title_short	Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.
title_full	Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.
title_fullStr	Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.
title_full_unstemmed	Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.
title_sort	control of m. tuberculosis esat-6 secretion and specific t cell recognition by phop.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/b6751aedc31a4e9cbe618a67b8fd11cd
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Control of M. tuberculosis ESAT-6 secretion and specific T cell recognition by PhoP.

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