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.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Akbar
authors.initials: A
authors.lastname: Kanji
authors.affiliation: Aga Khan University, Karachi, Pakistan. Electronic address: zahra.hasan@aku.edu.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Asho
authors.initials: A
authors.lastname: Ali
authors.affiliation: London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.affiliation: London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Mallard
authors.affiliation: London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom.
authors.forename: Francesc
authors.initials: F
authors.lastname: Coll
authors.affiliation: Pathogen Genomics Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Sydney Emerging Infections and Biosecurity Institute and School of Public Health, Sydney Medical School, University of Sydney, NSW 2006, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Hill-Cawthorne
authors.affiliation: Pathogen Genomics Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
authors.forename: Mridul
authors.initials: M
authors.lastname: Nair
authors.affiliation: London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom.
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Ambreen
authors.initials: A
authors.lastname: Zaver
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Sana
authors.initials: S
authors.lastname: Jafri
authors.affiliation: Aga Khan University, Karachi, Pakistan.
authors.forename: Rumina
authors.initials: R
authors.lastname: Hasan
mesh_terms: D004269:DNA, Bacterial / Q000032:analysis; D054908:Extensively Drug-Resistant Tuberculosis / Q000145:classification / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D054643:INDEL Mutation; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial
keywords: Mycobacterium tuberculosis; PE_PGRS genes; Whole genome sequencing