Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis

Abstract The development of the latent phenotype of Mycobacterium tuberculosis (Mtb) in the human lungs is the major hurdle to eradicate Tuberculosis. We recently reported that exposure to nitrite (10 mM) for six days under in vitro aerobic conditions completely transforms the bacilli into a viable...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sonia Agrawal, Suwarna Gample, Amar Yeware, Dhiman Sarkar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e24ff14468174d28abff76d5eb5f975c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e24ff14468174d28abff76d5eb5f975c
record_format	dspace
spelling	oai:doaj.org-article:e24ff14468174d28abff76d5eb5f975c2021-12-02T18:37:12ZNovel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis10.1038/s41598-021-99346-12045-2322https://doaj.org/article/e24ff14468174d28abff76d5eb5f975c2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99346-1https://doaj.org/toc/2045-2322Abstract The development of the latent phenotype of Mycobacterium tuberculosis (Mtb) in the human lungs is the major hurdle to eradicate Tuberculosis. We recently reported that exposure to nitrite (10 mM) for six days under in vitro aerobic conditions completely transforms the bacilli into a viable but non-cultivable phenotype. Herein, we show that nitrite (beyond 5 mM) treated Mtb produces nitric oxide (NO) within the cell in a dose-dependent manner. Our search for the conserved sequence of NO synthesizing enzyme in the bacterial system identified MRA2164 and MRA0854 genes, of which the former was found to be significantly up regulated after nitrite exposure. In addition, the purified recombinant MRA2164 protein shows significant nitrite dependent NO synthesizing activity. The knockdown of the MRA2164 gene at mRNA level expression resulted in a significantly reduced NO level compared to the wild type bacilli with a simultaneous return of its replicative capability. Therefore, this study first time reports that nitrite induces dormancy in Mtb cells through induced expression of the MRA2164 gene and productions of NO as a mechanism for maintaining non-replicative stage in Mtb. This observation could help to control the Tuberculosis disease, especially the latent phenotype of the bacilli.Sonia AgrawalSuwarna GampleAmar YewareDhiman SarkarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sonia Agrawal Suwarna Gample Amar Yeware Dhiman Sarkar Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
description	Abstract The development of the latent phenotype of Mycobacterium tuberculosis (Mtb) in the human lungs is the major hurdle to eradicate Tuberculosis. We recently reported that exposure to nitrite (10 mM) for six days under in vitro aerobic conditions completely transforms the bacilli into a viable but non-cultivable phenotype. Herein, we show that nitrite (beyond 5 mM) treated Mtb produces nitric oxide (NO) within the cell in a dose-dependent manner. Our search for the conserved sequence of NO synthesizing enzyme in the bacterial system identified MRA2164 and MRA0854 genes, of which the former was found to be significantly up regulated after nitrite exposure. In addition, the purified recombinant MRA2164 protein shows significant nitrite dependent NO synthesizing activity. The knockdown of the MRA2164 gene at mRNA level expression resulted in a significantly reduced NO level compared to the wild type bacilli with a simultaneous return of its replicative capability. Therefore, this study first time reports that nitrite induces dormancy in Mtb cells through induced expression of the MRA2164 gene and productions of NO as a mechanism for maintaining non-replicative stage in Mtb. This observation could help to control the Tuberculosis disease, especially the latent phenotype of the bacilli.
format	article
author	Sonia Agrawal Suwarna Gample Amar Yeware Dhiman Sarkar
author_facet	Sonia Agrawal Suwarna Gample Amar Yeware Dhiman Sarkar
author_sort	Sonia Agrawal
title	Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
title_short	Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
title_full	Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
title_fullStr	Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
title_full_unstemmed	Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis
title_sort	novel gene similar to nitrite reductase (no forming) plays potentially important role in the latency of tuberculosis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e24ff14468174d28abff76d5eb5f975c
work_keys_str_mv	AT soniaagrawal novelgenesimilartonitritereductasenoformingplayspotentiallyimportantroleinthelatencyoftuberculosis AT suwarnagample novelgenesimilartonitritereductasenoformingplayspotentiallyimportantroleinthelatencyoftuberculosis AT amaryeware novelgenesimilartonitritereductasenoformingplayspotentiallyimportantroleinthelatencyoftuberculosis AT dhimansarkar novelgenesimilartonitritereductasenoformingplayspotentiallyimportantroleinthelatencyoftuberculosis
_version_	1718377832963375104

Novel gene similar to nitrite reductase (NO forming) plays potentially important role in the latency of tuberculosis

Ejemplares similares