title: Variation of the Mycobacterium tuberculosis PE_PGRS 33 gene among clinical isolates.
abstract: PE_PGRS 33, one of about 60 PE_PGRS genes in the Mycobacterium tuberculosis genome, encodes a surface-expressed protein that may be involved in the antigenic variation of M. tuberculosis strains and evasion of the host immune system. While genetic differences between the PE_PGRS 33 genes of H37Rv and CDC 1551 have been noted, genetic variation in this gene among clinical isolates has not been evaluated. In order to gain a better understanding of the genetic basis for the role of PE_PGRS in antigenic variation and evasion of the host immune system, we investigated the genetic diversity of the PE_PGRS 33 gene among 123 clinical M. tuberculosis isolates from a population-based study, using PCR and DNA sequencing. The 123 isolates belonged to principal genetic groups 1, 2, and 3 and had IS 6110 copy numbers ranging from 1 to 22. Eighty-four (68.3%) of the 123 isolates were found to have at least one sequence variation in the PE_PGRS 33 gene, relative to that of H37Rv. Twenty-five different sequence variations were observed and included three insertions (ranging from 9 to 87 bp), nine deletions (ranging from 1 to 273 bp), one insertion-and-deletion event, and 12 single-nucleotide polymorphisms (six synonymous and six nonsynonymous). Analysis of the relationships among the different PE_PGRS 33 gene sequence variations suggests that polymorphisms in the gene are shifting along evolutionary lineages. The observed genetic diversity of the PE_PGRS 33 gene supports its role in antigenic variation and can serve as a basis for future investigations of the function of the PE_PGRS 33 gene among clinical isolates.
authors.affiliation: Epidemiology Department, School of Public Health, University of Michigan, 109 S. Observatory Street, Ann Arbor, MI 48109-2029, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Talarico
authors.forename: M Donald
authors.initials: MD
authors.lastname: Cave
authors.forename: Carl F
authors.initials: CF
authors.lastname: Marrs
authors.forename: Betsy
authors.initials: B
authors.lastname: Foxman
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis; D017353:Gene Deletion; D014644:Genetic Variation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D016254:Mutagenesis, Insertional; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D008565:Membrane Proteins; C440642:PE-PGRS protein, Mycobacterium