Characterization of genomic variations in SNPs of PE_PGRS genes reveals deletions and insertions in extensively drug resistant (XDR) M. tuberculosis strains from Pakistan

Handle URI:
http://hdl.handle.net/10754/552321
Title:
Characterization of genomic variations in SNPs of PE_PGRS genes reveals deletions and insertions in extensively drug resistant (XDR) M. tuberculosis strains from Pakistan
Authors:
Kanji, Akbar; Hasan, Zahra ( 0000-0001-7580-372X ) ; Ali, Asho; McNerney, Ruth; Mallard, Kim; Coll, Francesc; Hill-Cawthorne, Grant A. ( 0000-0002-3828-5473 ) ; Nair, Mridul; Clark, Taane G.; Zaver, Ambreen ( 0000-0002-7094-6040 ) ; Jafri, Sana; Hasan, Rumina
Abstract:
Background Mycobacterium tuberculosis (MTB) PE_PGRS genes belong to the PE multigene family. Although the function of PE_PGRS genes is unknown, it is hypothesized that the PE_PGRS genes may be associated with antigenic variability in MTB. Material and methods Whole genome sequencing analysis was performed on (n = 37) extensively drug-resistant (XDR) MTB strains from Pakistan, which included Lineage 1 (East African Indian, n = 2); Other lineage 1 (n = 3); Lineage 3 (Central Asian, n = 24); Other lineage 3 (n = 4); Lineage 4 (X3, n = 1) and T group (n = 3) MTB strains. Results There were 107 SNPs identified from the analysis of 42 PE_PGRS genes; of these, 13 were non-synonymous SNPs (nsSNPs). The nsSNPs identified in PE_PGRS genes – 6, 9 and 10 – were common in all EAI, CAS, Other lineages (1 and 3), T1 and X3. Deletions (DELs) in PE_PGRS genes – 3 and 19 – were observed in 17 (80.9%) CAS1 and 6 (85.7%) in Other lineages (1 and 3) XDR MTB strains, while DELs in the PE_PGRS49 were observed in all CAS1, CAS, CAS2 and Other lineages (1 and 3) XDR MTB strains. All CAS, EAI and Other lineages (1 and 3) strains showed insertions (INS) in PE_PGRS6 gene, while INS in the PE_PGRS genes 19 and 33 were observed in 20 (95.2%) CAS1, all CAS, CAS2, EAI and Other lineages (1 and 3) XDR MTB strains. Conclusion Genetic diversity in PE_PGRS genes contributes to antigenic variability and may result in increased immunogenicity of strains. This is the first study identifying variations in nsSNPs and INDELs in the PE_PGRS genes of XDR-TB strains from Pakistan. It highlights common genetic variations which may contribute to persistence.
KAUST Department:
Pathogen Genomics Laboratory
Citation:
Characterization of genomic variations in SNPs of PE_PGRS genes reveals deletions and insertions in extensively drug resistant (XDR) M. tuberculosis strains from Pakistan 2015, 4 (1):73 International Journal of Mycobacteriology
Publisher:
Elsevier BV
Journal:
International Journal of Mycobacteriology
Issue Date:
21-Jan-2015
DOI:
10.1016/j.ijmyco.2014.11.049
Type:
Article
ISSN:
22125531
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S2212553115000126
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Articles

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DC FieldValue Language
dc.contributor.authorKanji, Akbaren
dc.contributor.authorHasan, Zahraen
dc.contributor.authorAli, Ashoen
dc.contributor.authorMcNerney, Ruthen
dc.contributor.authorMallard, Kimen
dc.contributor.authorColl, Francescen
dc.contributor.authorHill-Cawthorne, Grant A.en
dc.contributor.authorNair, Mridulen
dc.contributor.authorClark, Taane G.en
dc.contributor.authorZaver, Ambreenen
dc.contributor.authorJafri, Sanaen
dc.contributor.authorHasan, Ruminaen
dc.date.accessioned2015-05-05T14:38:45Zen
dc.date.available2015-05-05T14:38:45Zen
dc.date.issued2015-01-21en
dc.identifier.citationCharacterization of genomic variations in SNPs of PE_PGRS genes reveals deletions and insertions in extensively drug resistant (XDR) M. tuberculosis strains from Pakistan 2015, 4 (1):73 International Journal of Mycobacteriologyen
dc.identifier.issn22125531en
dc.identifier.doi10.1016/j.ijmyco.2014.11.049en
dc.identifier.urihttp://hdl.handle.net/10754/552321en
dc.description.abstractBackground Mycobacterium tuberculosis (MTB) PE_PGRS genes belong to the PE multigene family. Although the function of PE_PGRS genes is unknown, it is hypothesized that the PE_PGRS genes may be associated with antigenic variability in MTB. Material and methods Whole genome sequencing analysis was performed on (n = 37) extensively drug-resistant (XDR) MTB strains from Pakistan, which included Lineage 1 (East African Indian, n = 2); Other lineage 1 (n = 3); Lineage 3 (Central Asian, n = 24); Other lineage 3 (n = 4); Lineage 4 (X3, n = 1) and T group (n = 3) MTB strains. Results There were 107 SNPs identified from the analysis of 42 PE_PGRS genes; of these, 13 were non-synonymous SNPs (nsSNPs). The nsSNPs identified in PE_PGRS genes – 6, 9 and 10 – were common in all EAI, CAS, Other lineages (1 and 3), T1 and X3. Deletions (DELs) in PE_PGRS genes – 3 and 19 – were observed in 17 (80.9%) CAS1 and 6 (85.7%) in Other lineages (1 and 3) XDR MTB strains, while DELs in the PE_PGRS49 were observed in all CAS1, CAS, CAS2 and Other lineages (1 and 3) XDR MTB strains. All CAS, EAI and Other lineages (1 and 3) strains showed insertions (INS) in PE_PGRS6 gene, while INS in the PE_PGRS genes 19 and 33 were observed in 20 (95.2%) CAS1, all CAS, CAS2, EAI and Other lineages (1 and 3) XDR MTB strains. Conclusion Genetic diversity in PE_PGRS genes contributes to antigenic variability and may result in increased immunogenicity of strains. This is the first study identifying variations in nsSNPs and INDELs in the PE_PGRS genes of XDR-TB strains from Pakistan. It highlights common genetic variations which may contribute to persistence.en
dc.publisherElsevier BVen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S2212553115000126en
dc.rightsArchived with thanks to International Journal of Mycobacteriology. http://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectWhole genome sequencingen
dc.subjectMycobacterium tuberculosisen
dc.subjectPE_PGRS genesen
dc.titleCharacterization of genomic variations in SNPs of PE_PGRS genes reveals deletions and insertions in extensively drug resistant (XDR) M. tuberculosis strains from Pakistanen
dc.typeArticleen
dc.contributor.departmentPathogen Genomics Laboratoryen
dc.identifier.journalInternational Journal of Mycobacteriologyen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionAga Khan University, Karachi, Pakistanen
dc.contributor.institutionLondon School of Hygiene and Tropical Medicine (LSHTM), United Kingdomen
dc.contributor.institutionSydney Emerging Infections and Biosecurity Institute and School of Public Health, Sydney Medical School, University of Sydney, NSW 2006, Australiaen
kaust.authorHill-Cawthorne, Grant A.en
kaust.authorNair, Mridulen
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