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Journal of Clinical Microbiology, October 2005, p. 4954-4960, Vol. 43, No. 10
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.10.4954-4960.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Variation of the Mycobacterium tuberculosis PE_PGRS33 Gene among Clinical Isolates

Sarah Talarico,1 M. Donald Cave,2,3 Carl F. Marrs,1 Betsy Foxman,1 Lixin Zhang,1 and Zhenhua Yang1*

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan,1 Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences,2 Central Arkansas Veterans Healthcare Center, Little Rock, Arkansas3

Received 11 May 2005/ Returned for modification 16 June 2005/ Accepted 5 July 2005

PE_PGRS33, 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_PGRS33 genes of H37Rv and CDC1551 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_PGRS33 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 IS6110 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_PGRS33 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_PGRS33 gene sequence variations suggests that polymorphisms in the gene are shifting along evolutionary lineages. The observed genetic diversity of the PE_PGRS33 gene supports its role in antigenic variation and can serve as a basis for future investigations of the function of the PE_PGRS33 gene among clinical isolates.

* Corresponding author. Mailing address: Epidemiology Department, School of Public Health, University of Michigan, 109 S. Observatory Street, Ann Arbor, MI 48109-2029. Phone: (734) 763-4296. Fax: (734) 764-3192. E-mail: zhenhua{at}umich.edu.

Journal of Clinical Microbiology, October 2005, p. 4954-4960, Vol. 43, No. 10
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.10.4954-4960.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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