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

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    Type
    Article
    Authors
    Kanji, Akbar
    Hasan, Zahra cc
    Ali, Asho
    McNerney, Ruth cc
    Mallard, Kim
    Coll, Francesc cc
    Hill-Cawthorne, Grant A. cc
    Nair, Mridul
    Clark, Taane G. cc
    Zaver, Ambreen cc
    Jafri, Sana
    Hasan, Rumina
    KAUST Department
    Bioscience Program
    Computational Bioscience Research Center (CBRC)
    Pathogen Genomics Laboratory
    Date
    2015-01-21
    Online Publication Date
    2015-01-21
    Print Publication Date
    2015-03
    Permanent link to this record
    http://hdl.handle.net/10754/552321
    
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    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.
    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
    Medknow
    Journal
    International Journal of Mycobacteriology
    DOI
    10.1016/j.ijmyco.2014.11.049
    PubMed ID
    26655202
    Additional Links
    http://linkinghub.elsevier.com/retrieve/pii/S2212553115000126
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ijmyco.2014.11.049
    Scopus Count
    Collections
    Articles; Bioscience Program; Computational Bioscience Research Center (CBRC)

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