Whole genome sequencing for the management of drug-resistant TB in low income high TB burden settings: Challenges and implications

Tuberculosis ◽  
2017 ◽  
Vol 107 ◽  
pp. 137-143 ◽  
Author(s):  
Sharana Mahomed ◽  
Kogieleum Naidoo ◽  
Navisha Dookie ◽  
Nesri Padayatchi
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Low Income ◽  
Whole Genome ◽  
Drug Resistant

scholarly journals Low-level rifampin resistance and rpoB mutations in Mycobacterium tuberculosis: An analysis of whole-genome sequencing and drug susceptibility test data in New York

2020 ◽  
Author(s):  
Joseph Shea ◽  
Tanya A. Halse ◽  
Donna Kohlerschmidt ◽  
Pascal Lapierre ◽  
Herns A. Modestil ◽  
...  
Keyword(s):  
New York ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Critical Concentration ◽  
Gene Sequencing ◽  
Drug Susceptibility ◽  
Whole Genome ◽  
Drug Resistant ◽  
Low Level ◽  
Indicator Tube

Rapid and reliable detection of rifampin (RIF) resistance is critical for the diagnosis and treatment of drug-resistant and multi-drug resistant (MDR) tuberculosis. Discordant RIF phenotype/genotype susceptibility results remain a challenge due to the presence of rpoB mutations which do not confer high levels of RIF resistance as have been exhibited in strains with mutations such as Ser450Leu. These strains, termed low-level RIF resistant, exhibit elevated RIF minimum inhibitory concentrations (MICs) compared to fully susceptible strains, however remain phenotypically susceptible by mycobacteria growth indicator tube (MGIT) testing and have been associated with poor patient outcomes. Here we assess RIF resistance prediction by whole-genome sequencing (WGS) among a set of 1779 prospectively tested strains by both prevalence of rpoB gene mutation and phenotype as part of routine clinical testing during a 21/2-year period. During this time, 139 strains were found to have nonsynonymous rpoB mutations, 53 of which were associated with RIF resistance, including both low-level and high-level resistance. Resistance to RIF (1.0 μg/mL in MGIT) was identified in 43 (81.1%) isolates. The remaining 10 (18.9%) strains were susceptible by MGIT, however were confirmed to be low-level RIF resistant by MIC testing. Full rpoB gene sequencing overcame the limitations of critical concentration phenotyping, probe-based genotyping, and partial-gene sequencing methods. Universal clinical WGS with concurrent phenotypic testing provided a more complete understanding of the prevalence and type of rpoB mutations and their association with RIF resistance in New York.

Extensively drug-resistant Acinetobacter baumannii isolated from intensive care units in northern Italy: a genomic approach to characterize new sequence types

2019 ◽  
Vol 14 (15) ◽  
pp. 1281-1292 ◽  
Author(s):  
Giovanni Lorenzin ◽  
Erika Scaltriti ◽  
Franco Gargiulo ◽  
Francesca Caccuri ◽  
Giorgio Piccinelli ◽  
...  
Keyword(s):  
Intensive Care ◽  
Whole Genome Sequencing ◽  
Acinetobacter Baumannii ◽  
Intensive Care Units ◽  
Genome Sequencing ◽  
Multilocus Sequence Typing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Sequence Types

Aim: This study aims to characterize clinical strains of Acinetobacter baumannii with an extensively drug-resistant phenotype. Methods: VITEK® 2, Etest® method and broth microdilution method for colistin were used. PCR analysis and multilocus sequence typing Pasteur scheme were performed to identify bla-OXA genes and genetic relatedness, respectively. Whole-genome sequencing analysis was used to characterize three isolates. Results: All the isolates were susceptible only to polymyxins. blaOXA-23-like gene was the only acquired carbapenemase gene in 88.2% of the isolates. Multilocus sequence typing identified various sequence types: ST2, ST19, ST195, ST577 and ST632. Two new sequence types, namely, ST1279 and ST1280, were detected by whole-genome sequencing. Conclusion: This study showed that carbapenem-resistant A. baumannii isolates causing infections in intensive care units almost exclusively produce OXA-23, underlining their frequent spread in Italy.

scholarly journals Genome Sequencing of Polydrug-, Multidrug-, and Extensively Drug-Resistant Mycobacterium tuberculosis Strains from South India

2019 ◽  
Vol 8 (12) ◽  
Author(s):  
Sivakumar Shanmugam ◽  
Narender Kumar ◽  
Dina Nair ◽  
Mohan Natrajan ◽  
Srikanth Prasad Tripathy ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
South India ◽  
Sequence Data ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Extensively Drug Resistant

The genomes of 16 clinical Mycobacterium tuberculosis isolates were subjected to whole-genome sequencing to identify mutations related to resistance to one or more anti-Mycobacterium drugs. The sequence data will help in understanding the genomic characteristics of M. tuberculosis isolates and their resistance mutations prevalent in South India.

scholarly journals 799. Genetic Diversity of Mycobacterium tuberculosis Strains Causing Drug-Resistant Tuberculosis in Central Region of Mozambique: The Whole-Genome Sequencing

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S286-S287
Author(s):  
Evangelina Namburete
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Central Region ◽  
Disease Spread ◽  
Whole Genome ◽  
Drug Resistant ◽  
Illumina Hiseq ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis

Abstract Background Knowing the genetic diversity of M. tuberculosis strains causing drug-resistant tuberculosis (DR-TB) in high burden TB and low resources countries such as Mozambique is a key factor to TB disease spread control and world TB epidemic control. Whole-genome sequencing (WGS) better describes molecular diversity, lineages and sub lineages, relationship between strains, underline mutations conferring drug-resistant TB, which may not be shown by molecular and phenotypic tests. As far as we know this is the first study that describes genetic diversity of M. tuberculosis strains causing DR-TB and using WGS in central region of Mozambique.We aim to describe genetic diversity of M. tuberculosis strains causing DR-TB in central Mozambique. Methods A total of 35 strains from Beira Mozambique were evaluated with genotypic tests (Genotype MTBDRplus™, and MTBDRsl™); phenotypic (MGIT-SIRE™) and DST. All isolates resistant to isoniazid (H) or rifampicin (R) or both were submitted to WGS Illumina HiSeq 2000 and analyzed with TB profiler database and phylogenetic tree was done using Figtree tool. This was a descriptive cross-sectional study. Results WGS shown that strains analyzed, belongs to three of six major lineages, with Lineage 4: 25(71.4%); Lineage 1: 5(14.3%); and Lineage 2 Beijing family: 5(14.3%)]. All pre-XDR strains 3(8.6%) were from lineage 4.3. By WGS, all 35 strains had any mutations conferring DR-TB while in one strain, mutation was not shown by genotypic neither phenotypic DST. Compared with genotypic tests, WGS had best performance in showing mutation conferring resistance to etambutol 12/35 (34.3%) and 7/35 (20%). Conclusion The DR-TB disease in Beira Mozambique is mainly caused by M. tuberculosis strains of Lineage 4, sub-lineage 3 although lineage 1 and 2 are also present. WGS shows underline mutations causing DR–TB that are not detected by genotypic and phenotypic DST test. Disclosures All authors: No reported disclosures.

scholarly journals Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012–2016

2019 ◽  
Vol 25 (3) ◽  
pp. 538-546
Author(s):  
Imen Bouzouita ◽  
Andrea Maurizio Cabibbe ◽  
Alberto Trovato ◽  
Henda Daroui ◽  
Asma Ghariani ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant

scholarly journals A67 Use of next-generation whole-genome sequencing to understand drug-resistant Mycobacterium tuberculosis in Botswana

2018 ◽  
Vol 4 (suppl_1) ◽  
Author(s):  
T Iketleng ◽  
T Mogashoa ◽  
B Mbeha ◽  
L Letsibogo ◽  
J Makhema ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Next Generation

scholarly journals Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Thomas R Connor ◽  
Clare R Barker ◽  
Kate S Baker ◽  
François-Xavier Weill ◽  
Kaisar Ali Talukder ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Low Income ◽  
Shigella Flexneri ◽  
Virulence Gene ◽  
Low Income Countries ◽  
Whole Genome ◽  
Phylogenetic Groups ◽  
Gene Acquisition ◽  
History Of

Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.

scholarly journals Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0117771 ◽  
Author(s):  
Asho Ali ◽  
Zahra Hasan ◽  
Ruth McNerney ◽  
Kim Mallard ◽  
Grant Hill-Cawthorne ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Drug Resistant ◽  
Extensively Drug Resistant
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