Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria

Abstract Mycobacteria share with other actinomycetes the ability to produce large quantities of triacylglycerol (TAG), which accumulate as intracytoplasmic lipid inclusions (ILI) also known as lipid droplets (LD). Mycobacterium tuberculosis (M. tb), the etiologic agent of tuberculosis, acquires fatt...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pierre Santucci, Matt D. Johansen, Vanessa Point, Isabelle Poncin, Albertus Viljoen, Jean-François Cavalier, Laurent Kremer, Stéphane Canaan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eb69c7de1ea843358a1eaec12b8e4091
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:eb69c7de1ea843358a1eaec12b8e4091
record_format	dspace
spelling	oai:doaj.org-article:eb69c7de1ea843358a1eaec12b8e40912021-12-02T15:09:30ZNitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria10.1038/s41598-019-45164-52045-2322https://doaj.org/article/eb69c7de1ea843358a1eaec12b8e40912019-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45164-5https://doaj.org/toc/2045-2322Abstract Mycobacteria share with other actinomycetes the ability to produce large quantities of triacylglycerol (TAG), which accumulate as intracytoplasmic lipid inclusions (ILI) also known as lipid droplets (LD). Mycobacterium tuberculosis (M. tb), the etiologic agent of tuberculosis, acquires fatty acids from the human host which are utilized to synthesize TAG, subsequently stored in the form of ILI to meet the carbon and nutrient requirements of the bacterium during long periods of persistence. However, environmental factors governing mycobacterial ILI formation and degradation remain poorly understood. Herein, we demonstrated that in the absence of host cells, carbon excess and nitrogen starvation promote TAG accumulation in the form of ILI in M. smegmatis and M. abscessus, used as surrogate species of M. tb. Based on these findings, we developed a simple and reversible in vitro model to regulate ILI biosynthesis and hydrolysis in mycobacteria. We also showed that TAG formation is tgs1 dependent and that lipolytic enzymes mediate TAG breakdown. Moreover, we confirmed that the nitrogen-deprived and ILI-rich phenotype was associated with an increased tolerance towards several drugs used for treating mycobacterial infections. Importantly, we showed that the presence of ILI substantially enhanced the bacterial burden and granuloma abundance in zebrafish embryos infected with lipid-rich M. abscessus as compared to embryos infected with lipid-poor M. abscessus, suggesting that ILI are actively contributing to mycobacterial virulence and pathogenesis.Pierre SantucciMatt D. JohansenVanessa PointIsabelle PoncinAlbertus ViljoenJean-François CavalierLaurent KremerStéphane CanaanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-15 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierre Santucci Matt D. Johansen Vanessa Point Isabelle Poncin Albertus Viljoen Jean-François Cavalier Laurent Kremer Stéphane Canaan Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
description	Abstract Mycobacteria share with other actinomycetes the ability to produce large quantities of triacylglycerol (TAG), which accumulate as intracytoplasmic lipid inclusions (ILI) also known as lipid droplets (LD). Mycobacterium tuberculosis (M. tb), the etiologic agent of tuberculosis, acquires fatty acids from the human host which are utilized to synthesize TAG, subsequently stored in the form of ILI to meet the carbon and nutrient requirements of the bacterium during long periods of persistence. However, environmental factors governing mycobacterial ILI formation and degradation remain poorly understood. Herein, we demonstrated that in the absence of host cells, carbon excess and nitrogen starvation promote TAG accumulation in the form of ILI in M. smegmatis and M. abscessus, used as surrogate species of M. tb. Based on these findings, we developed a simple and reversible in vitro model to regulate ILI biosynthesis and hydrolysis in mycobacteria. We also showed that TAG formation is tgs1 dependent and that lipolytic enzymes mediate TAG breakdown. Moreover, we confirmed that the nitrogen-deprived and ILI-rich phenotype was associated with an increased tolerance towards several drugs used for treating mycobacterial infections. Importantly, we showed that the presence of ILI substantially enhanced the bacterial burden and granuloma abundance in zebrafish embryos infected with lipid-rich M. abscessus as compared to embryos infected with lipid-poor M. abscessus, suggesting that ILI are actively contributing to mycobacterial virulence and pathogenesis.
format	article
author	Pierre Santucci Matt D. Johansen Vanessa Point Isabelle Poncin Albertus Viljoen Jean-François Cavalier Laurent Kremer Stéphane Canaan
author_facet	Pierre Santucci Matt D. Johansen Vanessa Point Isabelle Poncin Albertus Viljoen Jean-François Cavalier Laurent Kremer Stéphane Canaan
author_sort	Pierre Santucci
title	Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
title_short	Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
title_full	Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
title_fullStr	Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
title_full_unstemmed	Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
title_sort	nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/eb69c7de1ea843358a1eaec12b8e4091
work_keys_str_mv	AT pierresantucci nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT mattdjohansen nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT vanessapoint nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT isabelleponcin nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT albertusviljoen nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT jeanfrancoiscavalier nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT laurentkremer nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria AT stephanecanaan nitrogendeprivationinducestriacylglycerolaccumulationdrugtoleranceandhypervirulenceinmycobacteria
_version_	1718387849976348672

Nitrogen deprivation induces triacylglycerol accumulation, drug tolerance and hypervirulence in mycobacteria

Ejemplares similares