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Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host

INTRODUCTION: Around 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to excl...

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Autores principales: Gómez-González, Paula Josefina, Grabowska, Anna D., Tientcheu, Leopold D., Tsolaki, Anthony G., Hibberd, Martin L., Campino, Susana, Phelan, Jody E., Clark, Taane G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591178/
https://www.ncbi.nlm.nih.gov/pubmed/37876785
http://dx.doi.org/10.3389/fmicb.2023.1244319
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author Gómez-González, Paula Josefina
Grabowska, Anna D.
Tientcheu, Leopold D.
Tsolaki, Anthony G.
Hibberd, Martin L.
Campino, Susana
Phelan, Jody E.
Clark, Taane G.
author_facet Gómez-González, Paula Josefina
Grabowska, Anna D.
Tientcheu, Leopold D.
Tsolaki, Anthony G.
Hibberd, Martin L.
Campino, Susana
Phelan, Jody E.
Clark, Taane G.
author_sort Gómez-González, Paula Josefina
collection PubMed
description INTRODUCTION: Around 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. Understanding the genetic diversity of pe/ppe families is essential to facilitate their potential translation into tools for tuberculosis prevention and treatment. METHODS: To investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis and M. bovis BCG. Individual pe/ppe gene alignments were extracted and diversity and conservation across the different lineages studied. RESULTS: The pe/ppe genes were classified into three groups based on the level of protein sequence conservation relative to H37Rv, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements, such as duplications and gene fusions, were observed between pe and pe_pgrs genes. Inter-lineage diversity revealed lineage-specific SNPs and indels. DISCUSSION: The high level of pe/ppe genes conservation, together with the lineage-specific findings, suggest their phylogenetic informativeness. However, structural variants and gene rearrangements differing from the reference were also identified, with potential implications for pathogenicity. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control.
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spelling pubmed-105911782023-10-24 Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host Gómez-González, Paula Josefina Grabowska, Anna D. Tientcheu, Leopold D. Tsolaki, Anthony G. Hibberd, Martin L. Campino, Susana Phelan, Jody E. Clark, Taane G. Front Microbiol Microbiology INTRODUCTION: Around 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. Understanding the genetic diversity of pe/ppe families is essential to facilitate their potential translation into tools for tuberculosis prevention and treatment. METHODS: To investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis and M. bovis BCG. Individual pe/ppe gene alignments were extracted and diversity and conservation across the different lineages studied. RESULTS: The pe/ppe genes were classified into three groups based on the level of protein sequence conservation relative to H37Rv, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements, such as duplications and gene fusions, were observed between pe and pe_pgrs genes. Inter-lineage diversity revealed lineage-specific SNPs and indels. DISCUSSION: The high level of pe/ppe genes conservation, together with the lineage-specific findings, suggest their phylogenetic informativeness. However, structural variants and gene rearrangements differing from the reference were also identified, with potential implications for pathogenicity. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control. Frontiers Media S.A. 2023-10-09 /pmc/articles/PMC10591178/ /pubmed/37876785 http://dx.doi.org/10.3389/fmicb.2023.1244319 Text en Copyright © 2023 Gómez-González, Grabowska, Tientcheu, Tsolaki, Hibberd, Campino, Phelan and Clark. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Gómez-González, Paula Josefina
Grabowska, Anna D.
Tientcheu, Leopold D.
Tsolaki, Anthony G.
Hibberd, Martin L.
Campino, Susana
Phelan, Jody E.
Clark, Taane G.
Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host
title Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host
title_full Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host
title_fullStr Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host
title_full_unstemmed Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host
title_short Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host
title_sort functional genetic variation in pe/ppe genes contributes to diversity in mycobacterium tuberculosis lineages and potential interactions with the human host
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591178/
https://www.ncbi.nlm.nih.gov/pubmed/37876785
http://dx.doi.org/10.3389/fmicb.2023.1244319
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