TY - JOUR
T1 - Characterization of genomic variations in SNPs of PE_PGRS genes reveals deletions and insertions in extensively drug resistant (XDR) M. tuberculosis strains from Pakistan
AU - Kanji, Akbar
AU - Hasan, Zahra
AU - Ali, Asho
AU - McNerney, Ruth
AU - Mallard, Kim
AU - Coll, Francesc
AU - Hill-Cawthorne, Grant
AU - Nair, Mridul
AU - Clark, Taane G.
AU - Zaver, Ambreen
AU - Jafri, Sana
AU - Hasan, Rumina
N1 - Publisher Copyright:
© 2015 Asian African Society for Mycobacteriology.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - 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.
AB - 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.
KW - Mycobacterium tuberculosis
KW - PE_PGRS genes
KW - Whole genome sequencing
UR - http://www.scopus.com/inward/record.url?scp=84923967845&partnerID=8YFLogxK
U2 - 10.1016/j.ijmyco.2014.11.049
DO - 10.1016/j.ijmyco.2014.11.049
M3 - Article
C2 - 26655202
AN - SCOPUS:84923967845
SN - 2212-5531
VL - 4
SP - 73
EP - 79
JO - International Journal of Mycobacteriology
JF - International Journal of Mycobacteriology
IS - 1
ER -