Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.

Findings from previous comparative genomics studies of the Mycobacterium tuberculosis complex (MTBC) suggest genomic variation among the genotypes may have phenotypic implications. We investigated the diversity in the phenotypic profiles of the main prevalent MTBC genotypes in West Africa. Thirty-si...

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Autores principales: Stephen Osei-Wusu, Isaac Darko Otchere, Portia Morgan, Abdul Basit Musah, Ishaque Mintah Siam, Diana Asandem, Theophilus Afum, Prince Asare, Adwoa Asante-Poku, Kwadwo Asamoah Kusi, Sebastien Gagneux, Dorothy Yeboah-Manu
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Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/d0f624d9f08c442388db9b0fce70463d
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spelling oai:doaj.org-article:d0f624d9f08c442388db9b0fce70463d2021-12-02T20:17:32ZGenotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.1932-620310.1371/journal.pone.0255433https://doaj.org/article/d0f624d9f08c442388db9b0fce70463d2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255433https://doaj.org/toc/1932-6203Findings from previous comparative genomics studies of the Mycobacterium tuberculosis complex (MTBC) suggest genomic variation among the genotypes may have phenotypic implications. We investigated the diversity in the phenotypic profiles of the main prevalent MTBC genotypes in West Africa. Thirty-six whole genome sequenced drug susceptible MTBC isolates belonging to lineages 4, 5 and 6 were included in this study. The isolates were phenotypically characterized for urease activity, tween hydrolysis, Thiophen-2-Carboxylic Acid Hydrazide (TCH) susceptibility, nitric oxide production, and growth rate in both liquid (7H9) and solid media (7H11 and Löwenstein-Jensen (L-J)). Lineage 4 isolates showed the highest growth rate in both liquid (p = 0.0003) and on solid (L-J) media supplemented with glycerol (p<0.001) or pyruvate (p = 0.005). L6 isolates optimally utilized pyruvate compared to glycerol (p<0.001), whereas L5 isolates grew similarly on both media (p = 0.05). Lineage 4 isolates showed the lowest average time to positivity (TTP) (p = 0.01; Average TTP: L4 = 15days, L5 = 16.7days, L6 = 29.7days) and the highest logCFU/mL (p = 0.04; average logCFU/mL L4 = 5.9, L5 = 5.0, L6 = 4.4) on 7H11 supplemented with glycerol, but there was no significant difference in growth on 7H11 supplemented with pyruvate (p = 0.23). The highest release of nitrite was recorded for L5 isolates, followed by L4 and L6 isolates. However, the reverse was observed in the urease activity for the lineages. All isolates tested were resistant to TCH except for one L6 isolate. Comparative genomic analyses revealed several mutations that might explain the diverse phenotypic profiles of these isolates. Our findings showed significant phenotypic diversity among the MTBC lineages used for this study.Stephen Osei-WusuIsaac Darko OtcherePortia MorganAbdul Basit MusahIshaque Mintah SiamDiana AsandemTheophilus AfumPrince AsareAdwoa Asante-PokuKwadwo Asamoah KusiSebastien GagneuxDorothy Yeboah-ManuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0255433 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Stephen Osei-Wusu
Isaac Darko Otchere
Portia Morgan
Abdul Basit Musah
Ishaque Mintah Siam
Diana Asandem
Theophilus Afum
Prince Asare
Adwoa Asante-Poku
Kwadwo Asamoah Kusi
Sebastien Gagneux
Dorothy Yeboah-Manu
Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.
description Findings from previous comparative genomics studies of the Mycobacterium tuberculosis complex (MTBC) suggest genomic variation among the genotypes may have phenotypic implications. We investigated the diversity in the phenotypic profiles of the main prevalent MTBC genotypes in West Africa. Thirty-six whole genome sequenced drug susceptible MTBC isolates belonging to lineages 4, 5 and 6 were included in this study. The isolates were phenotypically characterized for urease activity, tween hydrolysis, Thiophen-2-Carboxylic Acid Hydrazide (TCH) susceptibility, nitric oxide production, and growth rate in both liquid (7H9) and solid media (7H11 and Löwenstein-Jensen (L-J)). Lineage 4 isolates showed the highest growth rate in both liquid (p = 0.0003) and on solid (L-J) media supplemented with glycerol (p<0.001) or pyruvate (p = 0.005). L6 isolates optimally utilized pyruvate compared to glycerol (p<0.001), whereas L5 isolates grew similarly on both media (p = 0.05). Lineage 4 isolates showed the lowest average time to positivity (TTP) (p = 0.01; Average TTP: L4 = 15days, L5 = 16.7days, L6 = 29.7days) and the highest logCFU/mL (p = 0.04; average logCFU/mL L4 = 5.9, L5 = 5.0, L6 = 4.4) on 7H11 supplemented with glycerol, but there was no significant difference in growth on 7H11 supplemented with pyruvate (p = 0.23). The highest release of nitrite was recorded for L5 isolates, followed by L4 and L6 isolates. However, the reverse was observed in the urease activity for the lineages. All isolates tested were resistant to TCH except for one L6 isolate. Comparative genomic analyses revealed several mutations that might explain the diverse phenotypic profiles of these isolates. Our findings showed significant phenotypic diversity among the MTBC lineages used for this study.
format article
author Stephen Osei-Wusu
Isaac Darko Otchere
Portia Morgan
Abdul Basit Musah
Ishaque Mintah Siam
Diana Asandem
Theophilus Afum
Prince Asare
Adwoa Asante-Poku
Kwadwo Asamoah Kusi
Sebastien Gagneux
Dorothy Yeboah-Manu
author_facet Stephen Osei-Wusu
Isaac Darko Otchere
Portia Morgan
Abdul Basit Musah
Ishaque Mintah Siam
Diana Asandem
Theophilus Afum
Prince Asare
Adwoa Asante-Poku
Kwadwo Asamoah Kusi
Sebastien Gagneux
Dorothy Yeboah-Manu
author_sort Stephen Osei-Wusu
title Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.
title_short Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.
title_full Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.
title_fullStr Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.
title_full_unstemmed Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa.
title_sort genotypic and phenotypic diversity of mycobacterium tuberculosis complex genotypes prevalent in west africa.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/d0f624d9f08c442388db9b0fce70463d
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