In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type.
BACKGROUND: India has the highest estimated burden of tuberculosis in the world, accounting for 21% of all tuberculosis cases world-wide. However, due to lack of systematic analysis using multiple markers the available information on the genomic diversity of Mycobacterium tuberculosis in India is li...
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doaj-b973bb40dc07494d827125b6990e8e162020-11-25T01:12:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0142e454010.1371/journal.pone.0004540In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type.Ruth StavrumVithal Prasad MyneeduVirendra K AroraNiyaz AhmedHarleen M S GrewalBACKGROUND: India has the highest estimated burden of tuberculosis in the world, accounting for 21% of all tuberculosis cases world-wide. However, due to lack of systematic analysis using multiple markers the available information on the genomic diversity of Mycobacterium tuberculosis in India is limited. METHODOLOGY/PRINCIPAL FINDINGS: Thus, 65 M. tuberculosis isolates from New Delhi, India were analyzed by spoligotyping, MIRU-VNTR, large deletion PCR typing and single nucleotide polymorphism analysis (SNP). The Central Asian (CAS) 1 _DELHI sub-lineage was the most prevalent sub-lineage comprising 46.2% (n = 30) of all isolates, with shared-type (ST) 26 being the most dominant genotype comprising 24.6% (n = 16) of all isolates. Other sub-lineages observed were: East-African Indian (EAI)-5 (9.2%, n = 6), EAI6_BGD1 (6.2%, n = 4), EAI3_IND, CAS and T1 with 6.2% each (n = 4 each), Beijing (4.6%, n = 3), CAS2 (3.1%, n = 2), and X1 and X2 with 1 isolate each. Genotyping results from five isolates (7.7%) did not match any existing spoligopatterns, and one isolate, ST124, belonged to an undefined lineage. Twenty-six percent of the isolates belonged to the TbD1+ PGG1 genogroup. SNP analysis of the pncA gene revealed a CAS-lineage specific silent mutation, S65S, which was observed for all CAS-lineage isolates (except two ST26 isolates) and in 1 orphan. Mutations in the pncA gene, conferring resistance to pyrazinamide, were observed in 15.4% of all isolates. Collectively, mutations in the rpoB gene, the katG gene and in both rpoB and katG genes, conferring resistance to rifampicin and isoniazid, respectively, were more frequent in CAS1_DELHI isolates compared to non-CAS_DELHI isolates (OR: 3.1, CI95% [1.11, 8.70], P = 0.045). The increased frequency of drug-resistance could not be linked to the patients' history of previous anti-tuberculosis treatment (OR: 1.156, CI95% [0.40, 3.36], P = 0.79). Fifty-six percent of all new tuberculosis patients had mutations in either the katG gene or the rpoB gene, or in both katG and rpoB genes. CONCLUSION: CAS1_DELHI isolates circulating in New Delhi, India have a high frequency of mutations in the rpoB and katG genes. A silent mutation (S65S) in the pncA gene can be used as a putative genetic marker for CAS-lineage isolates.http://europepmc.org/articles/PMC2641002?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ruth Stavrum Vithal Prasad Myneedu Virendra K Arora Niyaz Ahmed Harleen M S Grewal |
spellingShingle |
Ruth Stavrum Vithal Prasad Myneedu Virendra K Arora Niyaz Ahmed Harleen M S Grewal In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. PLoS ONE |
author_facet |
Ruth Stavrum Vithal Prasad Myneedu Virendra K Arora Niyaz Ahmed Harleen M S Grewal |
author_sort |
Ruth Stavrum |
title |
In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. |
title_short |
In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. |
title_full |
In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. |
title_fullStr |
In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. |
title_full_unstemmed |
In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. |
title_sort |
in-depth molecular characterization of mycobacterium tuberculosis from new delhi--predominance of drug resistant isolates of the 'modern' (tbd1) type. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-01-01 |
description |
BACKGROUND: India has the highest estimated burden of tuberculosis in the world, accounting for 21% of all tuberculosis cases world-wide. However, due to lack of systematic analysis using multiple markers the available information on the genomic diversity of Mycobacterium tuberculosis in India is limited. METHODOLOGY/PRINCIPAL FINDINGS: Thus, 65 M. tuberculosis isolates from New Delhi, India were analyzed by spoligotyping, MIRU-VNTR, large deletion PCR typing and single nucleotide polymorphism analysis (SNP). The Central Asian (CAS) 1 _DELHI sub-lineage was the most prevalent sub-lineage comprising 46.2% (n = 30) of all isolates, with shared-type (ST) 26 being the most dominant genotype comprising 24.6% (n = 16) of all isolates. Other sub-lineages observed were: East-African Indian (EAI)-5 (9.2%, n = 6), EAI6_BGD1 (6.2%, n = 4), EAI3_IND, CAS and T1 with 6.2% each (n = 4 each), Beijing (4.6%, n = 3), CAS2 (3.1%, n = 2), and X1 and X2 with 1 isolate each. Genotyping results from five isolates (7.7%) did not match any existing spoligopatterns, and one isolate, ST124, belonged to an undefined lineage. Twenty-six percent of the isolates belonged to the TbD1+ PGG1 genogroup. SNP analysis of the pncA gene revealed a CAS-lineage specific silent mutation, S65S, which was observed for all CAS-lineage isolates (except two ST26 isolates) and in 1 orphan. Mutations in the pncA gene, conferring resistance to pyrazinamide, were observed in 15.4% of all isolates. Collectively, mutations in the rpoB gene, the katG gene and in both rpoB and katG genes, conferring resistance to rifampicin and isoniazid, respectively, were more frequent in CAS1_DELHI isolates compared to non-CAS_DELHI isolates (OR: 3.1, CI95% [1.11, 8.70], P = 0.045). The increased frequency of drug-resistance could not be linked to the patients' history of previous anti-tuberculosis treatment (OR: 1.156, CI95% [0.40, 3.36], P = 0.79). Fifty-six percent of all new tuberculosis patients had mutations in either the katG gene or the rpoB gene, or in both katG and rpoB genes. CONCLUSION: CAS1_DELHI isolates circulating in New Delhi, India have a high frequency of mutations in the rpoB and katG genes. A silent mutation (S65S) in the pncA gene can be used as a putative genetic marker for CAS-lineage isolates. |
url |
http://europepmc.org/articles/PMC2641002?pdf=render |
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