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

Abstract

BackgroundLebanon 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.MethodsIsolates 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).ResultsThe 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.ConclusionsThe 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 materialThe online version of this article (10.1186/s12879-018-3626-3) contains supplementary material, which is available to authorized users.

Spoligotyping of Mycobacterium tuberculosis isolates using Luminex®-based method in Lebanon

“…Compared to a recent study from Lebanon, which characterized 13 MTB isolates by WGS, our findings showed close rates in the prevalence of lineage 4 (63% vs 53.8%) and lineage 2 (6% vs 7.7%), while higher rates of lineage 3 (24.5% vs 7.7%). However, no lineage 1 or M. bovis were detected among our isolates as was the case in the mentioned study (L1 and M. bovis, each at 15.4%) [19].…”

“…Sputum specimens were digested-decontaminated according to standard procedure, as reported earlier [2,3,19]. Briefly, the processed specimens were inoculated into both a Middlebrook 7H9 broth (Mycobacterial Growth Indicator Tube-MGIT, Merck, Darmstadt, Germany) and a solid-based medium (Löwenstein-Jensen, Merck, Darmstadt, Germany).…”

“…Several reports addressed the genotyping profiles of MTB isolates in different parts of the world, however, this characterization is scarce in Lebanon [18,19]. Hence, the goal of this study was to reveal the genotyping diversity of MTB complex strains in Lebanon.…”

Genomic and temporal analyses of Mycobacterium bovis in southern Brazil

“…In order to estimate a date for the introduction of CC Eu2 into RS, a global collection of 252 published Eu2 isolates was assembled [25,40,41,[72][73][74][75][76] (File S1). Quality control and mapping were performed as above and the isolates were combined with the 64 Eu2 isolates sequenced in this study.…”

Evaluation of the frequency of mutation genes in multidrug-resistant tuberculosis (MDR-TB) strains in Beijing, China

“…MDR-TB is defined as TB that is caused by M.tb resistant to at least the two most powerful anti-TB drugs, isoniazid (INH) and rifampin (RIF) [ 2 ]. Resistance to anti-TB drugs in M.tb mainly arises from genomic mutations in genes encoding either the drug target or enzymes involved in drug activation [ 3 ].…”