Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics

Abstract Whole genome sequencing (WGS) is able to differentiate closely related Mycobacterium tuberculosis variants within the same transmission cluster. Our aim was to evaluate if this higher discriminatory power may help identify and characterize more actively transmitted variants and understand t...

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Autores principales:	Estefanía Abascal, Charlotte Genestet, Ana Valera, Marta Herranz, Miguel Martinez-Lirola, Patricia Muñoz, Oana Dumitrescu, Darío García de Viedma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c23b5395c6e04dd5a68f949f66985a22
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spelling	oai:doaj.org-article:c23b5395c6e04dd5a68f949f66985a222021-12-02T14:47:38ZAssessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics10.1038/s41598-021-90568-x2045-2322https://doaj.org/article/c23b5395c6e04dd5a68f949f66985a222021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90568-xhttps://doaj.org/toc/2045-2322Abstract Whole genome sequencing (WGS) is able to differentiate closely related Mycobacterium tuberculosis variants within the same transmission cluster. Our aim was to evaluate if this higher discriminatory power may help identify and characterize more actively transmitted variants and understand the factors behind their success. We selected a robust MIRU-VNTR-defined cluster from Almería, Spain (22 cases throughout 2003–2019). WGS allowed discriminating, within the same epidemiological setting, between a successfully transmitted variant and seven closely related variants that did not lead to secondary cases, or were involved in self-limiting transmission (one single secondary case). Intramacrophagic growth of representative variants was evaluated in an in vitro infection model using U937 cells. Intramacrophage multiplication ratios (CFUs at Day 4/CFUs at Day 0) were higher for the actively transmitted variant (range 5.3–10.7) than for the unsuccessfully transmitted closely related variants (1.5–3.95). Two SNPs, mapping at the DNA binding domain of DnaA and at kdpD, were found to be specific of the successful variant.Estefanía AbascalCharlotte GenestetAna ValeraMarta HerranzMiguel Martinez-LirolaPatricia MuñozOana DumitrescuDarío García de ViedmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Estefanía Abascal Charlotte Genestet Ana Valera Marta Herranz Miguel Martinez-Lirola Patricia Muñoz Oana Dumitrescu Darío García de Viedma Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
description	Abstract Whole genome sequencing (WGS) is able to differentiate closely related Mycobacterium tuberculosis variants within the same transmission cluster. Our aim was to evaluate if this higher discriminatory power may help identify and characterize more actively transmitted variants and understand the factors behind their success. We selected a robust MIRU-VNTR-defined cluster from Almería, Spain (22 cases throughout 2003–2019). WGS allowed discriminating, within the same epidemiological setting, between a successfully transmitted variant and seven closely related variants that did not lead to secondary cases, or were involved in self-limiting transmission (one single secondary case). Intramacrophagic growth of representative variants was evaluated in an in vitro infection model using U937 cells. Intramacrophage multiplication ratios (CFUs at Day 4/CFUs at Day 0) were higher for the actively transmitted variant (range 5.3–10.7) than for the unsuccessfully transmitted closely related variants (1.5–3.95). Two SNPs, mapping at the DNA binding domain of DnaA and at kdpD, were found to be specific of the successful variant.
format	article
author	Estefanía Abascal Charlotte Genestet Ana Valera Marta Herranz Miguel Martinez-Lirola Patricia Muñoz Oana Dumitrescu Darío García de Viedma
author_facet	Estefanía Abascal Charlotte Genestet Ana Valera Marta Herranz Miguel Martinez-Lirola Patricia Muñoz Oana Dumitrescu Darío García de Viedma
author_sort	Estefanía Abascal
title	Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
title_short	Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
title_full	Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
title_fullStr	Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
title_full_unstemmed	Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
title_sort	assessment of closely related mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c23b5395c6e04dd5a68f949f66985a22
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Assessment of closely related Mycobacterium tuberculosis variants with different transmission success and in vitro infection dynamics

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