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Whole genome sequencing of Mycobacterium tuberculosis SB24 isolated from Sabah, Malaysia.

ABSTRACT: Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis (TB) that causes millions of death every year. We have sequenced the genome of M. tuberculosis isolated from cerebrospinal fluid (CSF) of a patient diagnosed with tuberculous meningitis (TBM). The isolated strain was referred as M. tuberculosis SB24. Genomic DNA of the M. tuberculosis SB24 was extracted and subjected to whole genome sequencing using PacBio platform. The draft genome size of M. tuberculosis SB24 was determined to be 4,452,489 bp with a G + C content of 65.6%. The whole genome shotgun project has been deposited in NCBI SRA under the accession number SRP076503.

SUBMITTER: Philip N

PROVIDER: S-EPMC4987507 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Whole genome sequencing of Mycobacterium tuberculosis SB24 isolated from Sabah, Malaysia.

Philip Noraini N Rodrigues Kenneth Francis KF William Timothy T John Daisy Vanitha DV

Genomics data 20160810

Mycobacterium tuberculosis (M. tuberculosis) is the causative agent of tuberculosis (TB) that causes millions of death every year. We have sequenced the genome of M. tuberculosis isolated from cerebrospinal fluid (CSF) of a patient diagnosed with tuberculous meningitis (TBM). The isolated strain was referred as M. tuberculosis SB24. Genomic DNA of the M. tuberculosis SB24 was extracted and subjected to whole genome sequencing using PacBio platform. The draft genome size of M. tuberculosis SB24 w ...[more]

PMID: 27556011

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Project description:Combating the spread of drug resistant tuberculosis is a global health priority. Whole genome association studies are being applied to identify genetic determinants of resistance to anti-tuberculosis drugs. Protein structure and interaction modelling are used to understand the functional effects of putative mutations and provide insight into the molecular mechanisms leading to resistance.To investigate the potential utility of these approaches, we analysed the genomes of 144 Mycobacterium tuberculosis clinical isolates from The Special Programme for Research and Training in Tropical Diseases (TDR) collection sourced from 20 countries in four continents. A genome-wide approach was applied to 127 isolates to identify polymorphisms associated with minimum inhibitory concentrations for first-line anti-tuberculosis drugs. In addition, the effect of identified candidate mutations on protein stability and interactions was assessed quantitatively with well-established computational methods.The analysis revealed that mutations in the genes rpoB (rifampicin), katG (isoniazid), inhA-promoter (isoniazid), rpsL (streptomycin) and embB (ethambutol) were responsible for the majority of resistance observed. A subset of the mutations identified in rpoB and katG were predicted to affect protein stability. Further, a strong direct correlation was observed between the minimum inhibitory concentration values and the distance of the mutated residues in the three-dimensional structures of rpoB and katG to their respective drugs binding sites.Using the TDR resource, we demonstrate the usefulness of whole genome association and convergent evolution approaches to detect known and potentially novel mutations associated with drug resistance. Further, protein structural modelling could provide a means of predicting the impact of polymorphisms on drug efficacy in the absence of phenotypic data. These approaches could ultimately lead to novel resistance mutations to improve the design of tuberculosis control measures, such as diagnostics, and inform patient management.

Project description:BackgroundTuberculosis (TB) is of high public health importance in Malaysia. Sabah State, located on the island of Borneo, has previously reported a particularly high burden of disease and faces unique contextual challenges compared with peninsular Malaysia. The aim of this study is to describe the epidemiology of TB in Sabah to identify risk groups and hotspots of TB transmission.MethodsWe conducted a retrospective review of TB cases notified in Sabah, Malaysia, between 2012 and 2018. Using data from the state's 'myTB' notification database, we calculated the case notification rate and described trends in the epidemiology, diagnostic practices and treatment outcomes of TB in Sabah within this period. The Chi-squared test was used for determining the difference between two proportions.ResultsBetween 2012 and 2018 there were 33 193 cases of TB reported in Sabah (128 cases per 100 000 population). We identified several geographic hotspots, including districts with > 200 cases per 100 000 population per year. TB rates increased with age and were highest in older males. Children < 15 years accounted for only 4.6% of cases. Moderate or advanced disease on chest X-ray and sputum smear positivity was high (58 and 81% of cases respectively), suggesting frequent late diagnosis. Multi-drug resistant (MDR) TB prevalence was low (0.3% of TB cases), however, rapid diagnostic test coverage was low (1.2%) and only 18% of all cases had a positive culture result. Treatment success was 83% (range: 81-85%) in those with drug-sensitive TB and 36% (range: 25-45%) in cases of MDR-TB.ConclusionBetween 2012 and 2018, TB notifications in Sabah State equated to 20% of Malaysia's total TB notifications, despite Sabah representing only 10% of Malaysia's population. We found hotspots of TB in urbanised population hubs and points of migration, as well as evidence of late presentation and diagnosis. Ensuring universal health coverage and expansion of GeneXpert® coverage is recommended to reduce barriers to care and early diagnosis and treatment for TB.

Dataset Information

Whole genome sequencing of Mycobacterium tuberculosis SB24 isolated from Sabah, Malaysia.

Publications

Whole genome sequencing of Mycobacterium tuberculosis SB24 isolated from Sabah, Malaysia.

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