title: Mycobacterium tuberculosis PE_PGRS16 and PE_PGRS26 genetic polymorphism among clinical isolates.
abstract: The Mycobacterium tuberculosis PE_PGRS multigene family is thought to be involved in antigenic variation, which can be generated by differential regulation of expression and a high frequency of genetic polymorphism. PE_PGRS16 and PE_PGRS26 are inversely regulated during persistent M. tuberculosis infection, suggesting that differential regulation of the expression of these two PE_PGRS genes may have a role in latency. To understand how genetic diversity, in addition to differential regulation, contributes to antigenic variability, we investigated the sequence variations in the PE_PGRS16 and PE_PGRS26 genes among 200 clinical M. tuberculosis strains, in comparison to the sequenced laboratory strain H37Rv, using PCR and DNA sequencing. Among the 200 strains, 102 (51%) and 100 (50%) had sequence variations within the PE_PGRS16 gene and the PE_PGRS26 gene, respectively. In-frame insertions and deletions, frameshifts, and SNPs were observed in both the PE_PGRS16 gene and the PE_PGRS26 gene. However, the frequency of frameshifts and in-frame deletions differed between the two PE_PGRS genes. Examining the profile of the PE_PGRS16, PE_PGRS26, and the previously investigated PE_PGRS33 amino acid sequences for each of the 200 strains, 72 different profiles were observed with frequencies ranging from 0.5% to 13%. In conclusion, a remarkable level of genetic diversity exists in the PE_PGRS16 and PE_PGRS26 genes of M. tuberculosis clinical strains. The significant sequence variations in the two PE_PGRS genes observed in this study could impact the function of these two PE_PGRS proteins and be associated with differences in the ability of the tubercle bacilli to remain persistent within the host.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, 109 S. Observatory Street, 4648 SPH I, Ann Arbor, MI 48109-2029, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Talarico
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.forename: Carl F
authors.initials: CF
authors.lastname: Marrs
authors.forename: Betsy
authors.initials: B
authors.lastname: Foxman
authors.forename: M Donald
authors.initials: MD
authors.lastname: Cave
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Brennan
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014397:Tuberculosis, Pulmonary / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008565:Membrane Proteins; C440642:PE-PGRS protein, Mycobacterium