scholarly journals Whole Genome Analysis of Extensively Drug Resistant Mycobacterium Tuberculosis Strains in Peru 

2020 ◽  
Author(s):  
Elias Santos Lázaro ◽  
Ronnie Gavilán Chávez ◽  
Lely Solari Zerpa ◽  
Aiko Vigo Tayro ◽  
Zully Puyén Guerra
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Multidrug Resistant ◽  
Annual Number ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Whole Genome Analysis ◽  
Evolutionary Patterns ◽  
Extensively Drug Resistant ◽  
Recent Transmission

Abstract Peru has the highest burden of multidrug-resistant tuberculosis in the Americas region, and since 1999, the annual number of extensively drug-resistant TB (XDR-TB) cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru.Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were due to mutations outside the hot spot regions analyzed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cutoff ≤ 10 SNPs revealed that only 23 (33.8%) strains were recent transmission events.This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.

scholarly journals Whole genome analysis of extensively drug resistant Mycobacterium tuberculosis strains in Peru

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
David Santos-Lazaro ◽  
Ronnie G. Gavilan ◽  
Lely Solari ◽  
Aiko N. Vigo ◽  
Zully M. Puyen
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Annual Number ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Whole Genome Analysis ◽  
Evolutionary Patterns ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

AbstractPeru has the highest burden of multidrug-resistant tuberculosis in the Americas region. Since 1999, the annual number of extensively drug-resistant tuberculosis (XDR-TB) Peruvian cases has been increasing, becoming a public health challenge. The objective of this study was to perform genomic characterization of Mycobacterium tuberculosis strains obtained from Peruvian patients with XDR-TB diagnosed from 2011 to 2015 in Peru. Whole genome sequencing (WGS) was performed on 68 XDR-TB strains from different regions of Peru. 58 (85.3%) strains came from the most populated districts of Lima and Callao. Concerning the lineages, 62 (91.2%) strains belonged to the Euro-American Lineage, while the remaining 6 (8.8%) strains belonged to the East-Asian Lineage. Most strains (90%) had high-confidence resistance mutations according to pre-established WHO-confident grading system. Discordant results between microbiological and molecular methodologies were caused by mutations outside the hotspot regions analysed by commercial molecular assays (rpoB I491F and inhA S94A). Cluster analysis using a cut-off ≤ 10 SNPs revealed that only 23 (34%) strains evidenced recent transmission links. This study highlights the relevance and utility of WGS as a high-resolution approach to predict drug resistance, analyse transmission of strains between groups, and determine evolutionary patterns of circulating XDR-TB strains in the country.

scholarly journals Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis

2012 ◽  
Vol 56 (6) ◽  
pp. 3047-3053 ◽  
Author(s):  
Lukas Fenner ◽  
Matthias Egger ◽  
Thomas Bodmer ◽  
Ekkehardt Altpeter ◽  
Marcel Zwahlen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Hot Spot ◽  
Multidrug Resistant ◽  
Beijing Genotype ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Content Type ◽  
Drug Resistance Mutations ◽  
Resistant Strains

ABSTRACTBacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistantMycobacterium tuberculosisisolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains,katGmutations were associated with high-level andinhApromoter mutations with low-level drug resistance. OnlykatG(S315T) (65.6% of all isoniazid-resistant strains) andinhApromoter −15C/T (22.7%) were found in molecular clusters.M. tuberculosislineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6;P< 0.0001). Lineage 1 was associated withinhApromoter −15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7;P= 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages;P< 0.0001). In conclusion,M. tuberculosisdrug resistance mutations were associated with various levels of drug resistance and transmission, andM. tuberculosislineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds inM. tuberculosisdrug resistance.

Metabolic profiles of multidrug resistant and extensively drug resistant Mycobacterium tuberculosis unveiled by metabolomics

Tuberculosis ◽  
2021 ◽  
Vol 126 ◽  
pp. 102043
Author(s):  
Amanda Mendes Rêgo ◽  
Duanne Alves da Silva ◽  
Nicole Victor Ferreira ◽  
Lucindo Cardoso de Pina ◽  
Joseph A.M. Evaristo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Metabolic Profiles ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Tuberculose Multirresistente por Estirpes da Família Beijing, em Doentes de Lisboa, Portugal: Estudo Preliminar

2017 ◽  
Vol 30 (3) ◽  
pp. 175 ◽  
Author(s):  
Fernando Maltez ◽  
Teresa Martins ◽  
Diana Póvoas ◽  
João Cabo ◽  
Helena Peres ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Past History ◽  
Multidrug Resistant ◽  
Resistance Pattern ◽  
Drug Resistant ◽  
Beijing Family ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Number Of Patients ◽  
Drug Resistant Strains

Introduction: Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known.Material and Methods: Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains.Results: Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients).Discussion: Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa.Conclusion: Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

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.

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