Cargando…

First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon

BACKGROUND: Lebanon hosts a heterogeneous population coming from underdeveloped and developing countries, resulting in increasing incidences of tuberculosis over the past years. The genetic heterogeneity and lineages associated with tuberculosis, along with their resistance determinants have not bee...

Descripción completa

Detalles Bibliográficos
Autores principales: Panossian, Balig, Salloum, Tamara, Araj, George F., Khazen, Georges, Tokajian, Sima
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311033/
https://www.ncbi.nlm.nih.gov/pubmed/30594126
http://dx.doi.org/10.1186/s12879-018-3626-3
_version_ 1783383539897597952
author Panossian, Balig
Salloum, Tamara
Araj, George F.
Khazen, Georges
Tokajian, Sima
author_facet Panossian, Balig
Salloum, Tamara
Araj, George F.
Khazen, Georges
Tokajian, Sima
author_sort Panossian, Balig
collection PubMed
description BACKGROUND: Lebanon hosts a heterogeneous population coming from underdeveloped and developing countries, resulting in increasing incidences of tuberculosis over the past years. The genetic heterogeneity and lineages associated with tuberculosis, along with their resistance determinants have not been studied at the genomic level previously in the region. METHODS: Isolates were recovered from the American University of Beirut Medical Center (AUBMC). Antimicrobial susceptibility profiles were determined using the MGIT automated system for the first-line drugs at AUBMC, while second-line drug susceptibility was tested at Mayo Clinic Laboratories. Whole Genome Sequencing (WGS) was performed to classify mycobacterial lineages and highlight single nucleotide mutations causing resistance to both 1st line and 2nd line antimicrobials. wgSNP analysis provided insights on the phylogeny of the isolates along with spoligotyping and core genomic SNVs, IS6110 insertion sites, and variable number tandem repeats (VNTR). RESULTS: The analyzed isolates carry distinct resistance determinants to isoniazid, rifampicin, ethambutol, quinolones, and streptomycin. The isolates belonged to different lineages including the Euro/American lineage (Lineage 4) (53.8%), M. bovis (15.4%) and Delhi/Central Asia (Lineage 1) (15.4%), Beijing/East Asia (Lineage 2) (7.7%), and East Africa/Indian Ocean lineage (Lineage 3) (7.7%) showing great phylogenetic differences at the genomic level. CONCLUSIONS: The population diversity in Lebanon holds an equally diverse and uncharacterized population of drug resistant mycobacteria. To achieve the WHO “END-TB” milestones of 2025 and 2035, Lebanon must decrease TB incidences by 95% in the next decade. This can only be done through WGS-based patient centered diagnosis with higher throughput and genomic resolution to improve treatment outcomes and to monitor transmission patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3626-3) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6311033
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-63110332019-01-07 First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon Panossian, Balig Salloum, Tamara Araj, George F. Khazen, Georges Tokajian, Sima BMC Infect Dis Research Article BACKGROUND: Lebanon hosts a heterogeneous population coming from underdeveloped and developing countries, resulting in increasing incidences of tuberculosis over the past years. The genetic heterogeneity and lineages associated with tuberculosis, along with their resistance determinants have not been studied at the genomic level previously in the region. METHODS: Isolates were recovered from the American University of Beirut Medical Center (AUBMC). Antimicrobial susceptibility profiles were determined using the MGIT automated system for the first-line drugs at AUBMC, while second-line drug susceptibility was tested at Mayo Clinic Laboratories. Whole Genome Sequencing (WGS) was performed to classify mycobacterial lineages and highlight single nucleotide mutations causing resistance to both 1st line and 2nd line antimicrobials. wgSNP analysis provided insights on the phylogeny of the isolates along with spoligotyping and core genomic SNVs, IS6110 insertion sites, and variable number tandem repeats (VNTR). RESULTS: The analyzed isolates carry distinct resistance determinants to isoniazid, rifampicin, ethambutol, quinolones, and streptomycin. The isolates belonged to different lineages including the Euro/American lineage (Lineage 4) (53.8%), M. bovis (15.4%) and Delhi/Central Asia (Lineage 1) (15.4%), Beijing/East Asia (Lineage 2) (7.7%), and East Africa/Indian Ocean lineage (Lineage 3) (7.7%) showing great phylogenetic differences at the genomic level. CONCLUSIONS: The population diversity in Lebanon holds an equally diverse and uncharacterized population of drug resistant mycobacteria. To achieve the WHO “END-TB” milestones of 2025 and 2035, Lebanon must decrease TB incidences by 95% in the next decade. This can only be done through WGS-based patient centered diagnosis with higher throughput and genomic resolution to improve treatment outcomes and to monitor transmission patterns. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12879-018-3626-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-12-29 /pmc/articles/PMC6311033/ /pubmed/30594126 http://dx.doi.org/10.1186/s12879-018-3626-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Panossian, Balig
Salloum, Tamara
Araj, George F.
Khazen, Georges
Tokajian, Sima
First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon
title First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon
title_full First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon
title_fullStr First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon
title_full_unstemmed First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon
title_short First insights on the genetic diversity of MDR Mycobacterium tuberculosis in Lebanon
title_sort first insights on the genetic diversity of mdr mycobacterium tuberculosis in lebanon
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311033/
https://www.ncbi.nlm.nih.gov/pubmed/30594126
http://dx.doi.org/10.1186/s12879-018-3626-3
work_keys_str_mv AT panossianbalig firstinsightsonthegeneticdiversityofmdrmycobacteriumtuberculosisinlebanon
AT salloumtamara firstinsightsonthegeneticdiversityofmdrmycobacteriumtuberculosisinlebanon
AT arajgeorgef firstinsightsonthegeneticdiversityofmdrmycobacteriumtuberculosisinlebanon
AT khazengeorges firstinsightsonthegeneticdiversityofmdrmycobacteriumtuberculosisinlebanon
AT tokajiansima firstinsightsonthegeneticdiversityofmdrmycobacteriumtuberculosisinlebanon