Dataset Information

Whole-Genome Sequencing and Annotation of a Drug-Resistant Extrapulmonary Clinical Isolate of Beijing Genotype Mycobacterium tuberculosis from Pune, India.

ABSTRACT: Whole-genome sequencing has emerged as a powerful tool to map genetic diversity among Mycobacterium tuberculosis isolates and identify the genomic signatures associated with drug resistance, pathogenesis, and disease transmission. Isolate LJ319 of the Mycobacterium tuberculosis complex (MTC)-Beijing genotype circulating in Maharashtra, India, which was obtained from the cerebrospinal fluid (CSF) of an immunocompetent patient, was subjected to whole-genome sequencing.

SUBMITTER: Hatolkar SM

PROVIDER: S-EPMC6013599 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Whole-Genome Sequencing and Annotation of a Drug-Resistant Extrapulmonary Clinical Isolate of Beijing Genotype Mycobacterium tuberculosis from Pune, India.

Hatolkar Swarupa M SM Misra Rabindra N RN Mahato Rajesh R Jadhav Savita S

Genome announcements 20180621 25

Whole-genome sequencing has emerged as a powerful tool to map genetic diversity among <i>Mycobacterium tuberculosis</i> isolates and identify the genomic signatures associated with drug resistance, pathogenesis, and disease transmission. Isolate LJ319 of the <i>Mycobacterium tuberculosis</i> complex (MTC)-Beijing genotype circulating in Maharashtra, India, which was obtained from the cerebrospinal fluid (CSF) of an immunocompetent patient, was subjected to whole-genome sequencing. ...[more]

PMID: 29930036

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Project description:The Beijing genotype is a lineage of Mycobacterium tuberculosis that is distributed worldwide and responsible for large epidemics, associated with multidrug-resistance. However, its distribution in Africa is less understood due to the lack of data. Our aim was to investigate the prevalence and possible transmission of Beijing strains in Mozambique by a multivariate analysis of genotypic, geographic and demographic data. A total of 543 M. tuberculosis isolates from Mozambique were spoligotyped. Of these, 33 were of the Beijing lineage. The genetic relationship between the Beijing isolates were studied by identification of genomic deletions within some Regions of Difference (RD), Restriction Fragment Length Polymorphism (RFLP) and Mycobacterial Interspersed Repetivie Unit - variable number tandem repeat (MIRU-VNTR). Beijing strains from South Africa, representing different sublineages were included as reference strains. The association between Beijing genotype, Human Immunodeficiency Virus (HIV) serology and baseline demographic data was investigated. HIV positive serostatus was significantly (p=0.023) more common in patients with Beijing strains than in patients with non-Beijing strains in a multivariable analysis adjusted for age, sex and province (14 (10.9%) of the 129 HIV positive patients had Beijing strains while 6/141 (4.3%) of HIV negative patients had Beijing strains). The majority of Beijing strains were found in the Southern region of Mozambique, particularly in Maputo City (17%). Only one Beijing strain was drug resistant (multi-drug resistant). By combined use of RD and spoligotyping, three genetic sublineages could be tentatively identified where a distinct group of four isolates had deletion of RD150, a signature of the "sublineage 7" recently emerging in South Africa. The same group was very similar to South African "sublineage 7" by RFLP and MIRU-VNTR, suggesting that this sublineage could have been recently introduced in Mozambique from South Africa, in association with HIV infection.

Project description:BackgroundThe most prevalent strains of Mycobacterium tuberculosis (M.tb) in Beijing belong to the Beijing genotype family. The influence of Beijing genotype prevalence on the development of drug resistance, and the association of infection with Beijing genotype M.tb with population characteristics, in Beijing, however, are still unclear.MethodsIn this retrospective study, 1189 isolates were subjected to drug susceptibility testing (DST) and molecular epidemiological analysis, and differences in the percentage of drug resistance between Beijing and non-Beijing genotype strains were compared. The association between the occurrence of drug resistance and the prevalence of Beijing genotype M.tb was analyzed using statistical methods.ResultsThe Beijing genotype family was the dominant genotype (83.3%) among the 1189 M.tb isolates. Beijing genotype M.tb strains were more likely to spread among males [p = 0.018, OR (95% CI):1.127(1.004-1.264)] and people in the 45-64 age group [p = 0.016, OR (95% CI): 1.438 (1.027-2.015)]. On the contrary, non-Beijing genotype M.tb strains were more probably disseminated among the over 65 [p = 0.005, OR (95% CI):0.653 (0.474-0.9)] and non-resident population [p = 0.035, OR (95% CI):1.185(0.985-1.427)]. DST results showed that 849 (71.4%) strains were fully sensitive to first-line drugs, while 340 (28.6%) strains were resistant to at least one drug, and 9% (107/1189) were MDR-TB. The frequency of INH-resistance among Beijing genotype strains was significantly lower than that among non-Beijing genotype strains (p = 0.032). In addition, the Beijing genotype family readily formed clusters.ConclusionsOur findings indicate that male and middle-aged people were more probably be infected by Beijing genotype M.tb, older people and non-residents were more probably be infected by non-Beijing genotype M.tb. The high percentage of resistance to INH occurring in non-Beijing genotype strains suggested that non-Beijing genotype strains should be given much more interest in Beijing.

Dataset Information

Whole-Genome Sequencing and Annotation of a Drug-Resistant Extrapulmonary Clinical Isolate of Beijing Genotype Mycobacterium tuberculosis from Pune, India.

Publications

Whole-Genome Sequencing and Annotation of a Drug-Resistant Extrapulmonary Clinical Isolate of Beijing Genotype Mycobacterium tuberculosis from Pune, India.

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