Dataset Information

The Rv3799-Rv3807 gene cluster in Mycobacterium tuberculosis genome corresponds to the 'Ancient Conserved Region' in CMN mycolyltransferases.

ABSTRACT: We have identified based on gene cluster analysis that the genes between Rv3799-Rv3807 in M. tuberculosis have orthologs in Corynebacteria, Mycobacteria and Nocardia (CMN) genomes. Therefore, this gene cluster possibly corresponds to the 'Ancient Conserved Region' of CMN mycolyltransferases. The evolutionary trace analysis suggests that twelve amino acid residues; Leu39, Trp51, Pro71, Trp82, Trp97, Phe100, Gly124, Ser126, Asp192, Glu230, Gly260 and Trp264 are 'absolutely conserved'. These amino acid residues constitute the active site and conserved hydrophobic tunnel in CMN mycolyltransferases.

SUBMITTER: Ramulu HG

PROVIDER: S-EPMC3089981 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature

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Publications

The Rv3799-Rv3807 gene cluster in Mycobacterium tuberculosis genome corresponds to the 'Ancient Conserved Region' in CMN mycolyltransferases.

Ramulu Hemalatha G HG Swathi Adindla A Guruprasad Lalitha L

Evolutionary bioinformatics online 20060101

We have identified based on gene cluster analysis that the genes between Rv3799-Rv3807 in M. tuberculosis have orthologs in Corynebacteria, Mycobacteria and Nocardia (CMN) genomes. Therefore, this gene cluster possibly corresponds to the 'Ancient Conserved Region' of CMN mycolyltransferases. The evolutionary trace analysis suggests that twelve amino acid residues; Leu39, Trp51, Pro71, Trp82, Trp97, Phe100, Gly124, Ser126, Asp192, Glu230, Gly260 and Trp264 are 'absolutely conserved'. These amino ...[more]

PMID: 21760704

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Project description:Tuberculosis (TB), caused by Mycobacterium tuberculosis bacteria, is a leading infectious cause of mortality worldwide, including in Pakistan. Drug resistant M. tuberculosis is an emerging threat for TB control, making it important to detect the underlying genetic mutations, and thereby inform treatment decision making and prevent transmission. Whole genome sequencing has emerged as the new diagnostic to reliably predict drug resistance within a clinically relevant time frame, and its deployment will have the greatest impact on TB control in highly endemic regions. To evaluate the mutations leading to drug resistance and to assess for evidence of the transmission of resistant strains, 81 M. tuberculosis samples from Khyber Pakhtunkhwa province (North West Pakistan) were subjected to whole genome sequencing and standard drug susceptibility testing for eleven anti-TB drugs. We found the majority of M. tuberculosis isolates were the CAS/Delhi strain-type (lineage 3; n = 57; 70.4%) and multi-drug resistant (MDR; n = 62; 76.5%). The most frequent resistance mutations were observed in the katG and rpoB genes, conferring resistance to isoniazid and rifampicin respectively. Mutations were also observed in genes conferring resistance to other first and second-line drugs, including in pncA (pyrazinamide), embB (ethambutol), gyrA (fluoroquinolones), rrs (aminoglycosides), rpsL, rrs and giB (streptomycin) loci. Whilst the majority of mutations have been reported in global datasets, we describe unreported putative resistance markers in katG, ethA (ethionamide), gyrA and gyrB (fluoroquinolones), and pncA. Analysis of the mutations revealed that acquisition of rifampicin resistance often preceded isoniazid in our isolates. We also observed a high proportion (17.6%) of pre-MDR isolates with fluoroquinolone resistance markers, potentially due to unregulated anti-TB drug use. Our isolates were compared to previously sequenced strains from Pakistan in a combined phylogenetic tree analysis. The presence of lineage 2 was only observed in our isolates. Using a cut-off of less than ten genome-wide mutation differences between isolates, a transmission analysis revealed 18 M. tuberculosis isolates clustering within eight networks, thereby providing evidence of drug-resistant TB transmission in the Khyber Pakhtunkhwa province. Overall, we have demonstrated that drug-resistant TB isolates are circulating and transmitted in North West Pakistan. Further, we have shown the usefulness of whole genome sequencing as a diagnostic tool for characterizing M. tuberculosis isolates, which will assist future epidemiological studies and disease control activities in Pakistan.

Dataset Information

The Rv3799-Rv3807 gene cluster in Mycobacterium tuberculosis genome corresponds to the 'Ancient Conserved Region' in CMN mycolyltransferases.

Publications

The Rv3799-Rv3807 gene cluster in Mycobacterium tuberculosis genome corresponds to the 'Ancient Conserved Region' in CMN mycolyltransferases.

Similar Datasets

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