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 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 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.

scholarly journals Draft Genome Sequences of Two Drug-Resistant Mycobacterium tuberculosis Isolates from Myanmar

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Htin Lin Aung ◽  
Thanda Tun ◽  
Elizabeth Permina ◽  
Wint Wint Nyunt ◽  
Si Thu Aung ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Draft Genome ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Genome Sequences ◽  
Health Concerns ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

Multidrug-resistant tuberculosis (MDR-TB) and lately, extensively drug-resistant TB (XDR-TB) are increasing global health concerns. Here, we present the genome sequences of two MDR-TB isolates from Myanmar, one of 27 countries with a high MDR-TB burden, and describe a number of mutations consistent with these being XDR-TB isolates.

scholarly journals Meropenem-Clavulanic Acid Has HighIn VitroActivity against Multidrug-Resistant Mycobacterium tuberculosis

2015 ◽  
Vol 59 (6) ◽  
pp. 3630-3632 ◽  
Author(s):  
L. Davies Forsman ◽  
C. G. Giske ◽  
J. Bruchfeld ◽  
T. Schön ◽  
P. Juréen ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Clavulanic Acid ◽  
Treatment Option ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Potential Treatment ◽  
Drug Resistant Tuberculosis ◽  
Content Type ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

ABSTRACTWe investigated the activity of meropenem-clavulanic acid (MEM-CLA) against 68Mycobacterium tuberculosisisolates. We included predominantly multi- and extensively drug-resistant tuberculosis (MDR/XDR-TB) isolates, since the activity of MEM-CLA for resistant isolates has previously not been studied extensively. Using Middlebrook 7H10 medium, all but four isolates showed an MIC distribution of 0.125 to 2 mg/liter for MEM-CLA, below the non-species-related breakpoint for MEM of 2 mg/liter defined by EUCAST. MEM-CLA is a potential treatment option for MDR/XDR-TB.

scholarly journals Whole-genome sequence analysis and comparisons between drug-resistance mutations and minimum inhibitory concentrations of Mycobacterium tuberculosis isolates causing M/XDR-TB

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244829
Author(s):  
Ditthawat Nonghanphithak ◽  
Orawee Kaewprasert ◽  
Pratchakan Chaiyachat ◽  
Wipa Reechaipichitkul ◽  
Angkana Chaiprasert ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Drug Resistant ◽  
Resistance Mutations ◽  
Tb 34 ◽  
Susceptibility Tests

Drug resistance (DR) remains a major challenge for tuberculosis (TB) control. Whole-genome sequencing (WGS) provides the highest genetic resolution for genotypic drug-susceptibility tests (DST). We compared DST profiles of 60 Mycobacterium tuberculosis isolates which were drug resistant according to agar proportion tests (one poly DR-TB, 34 multidrug-resistant TB and 25 extensively drug-resistant TB). We additionally performed minimum inhibitory concentration (MIC) tests using Sensititre MYCOTBI plates (MYCOTB) and a WGS-based DST. Agreement between WGS-based DST and MYCOTB was high for all drugs except ethambutol (65%) and ethionamide (62%). Isolates harboring the -15 c/t inhA promoter mutation had a significantly lower MIC for isoniazid than did isolates with the katG Ser315Thr mutation (p < 0.001). Similar patterns were seen for ethambutol (embB Gly406Asp vs. embB Met306Ile), streptomycin (gid Gly73Ala vs. rpsL Lys43Arg), moxifloxacin (gyrA Ala90Val vs. gyrA Asp94Gly) and rifabutin (rpoB Asp435Phe/Tyr/Val vs. rpoB Ser450Leu). For genotypic heteroresistance, isolates with lower proportion of mapped read tended to has lower MIC of anti-TB drugs than those with higher proportion. These results emphasize the high applicability of WGS for determination of DR-TB and the association of particular mutations with MIC levels.

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