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Journal of Clinical Microbiology, April 2009, p. 1002-1011, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.01313-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genomic Comparison of PE and PPE Genes in the Mycobacterium avium Complex{triangledown} ,{dagger}

Nick Mackenzie,1 David C. Alexander,2 Christine Y. Turenne,2 Marcel A. Behr,2 and Jeroen M. De Buck1*

Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada,1 Division of Infectious Diseases and Medical Microbiology, McGill University Health Center, Montreal General Hospital Research Institute, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada2

Received 10 July 2008/ Returned for modification 11 December 2008/ Accepted 3 January 2009

The Mycobacterium avium complex (MAC) comprises genomically similar but phenotypically divergent bacteria that inhabit diverse environments and that cause disease in different hosts. In this study, a whole-genome approach was used to examine the polymorphic PE (Pro-Glu) and PPE (Pro-Pro-Glu) gene families, implicated in immunostimulation and virulence. The four major groups of MAC organisms were examined, including the newly sequenced type strains of M. intracellulare and M. avium subsp. avium, plus M. avium subsp. paratuberculosis and M. avium subsp. hominissuis, for the purpose of finding genetic differences that could be exploited to design diagnostic tests specific to these groups and that could help explain their divergence in pathogenesis and host specificity. Unique and missing PPE genes were found in all MAC members except M. avium subsp. avium. Only M. intracellulare had a unique PE gene. Apart from this, most PE and PPE sequences were conserved, with average nucleotide sequence identities of 99.1 and 98.1%, respectively, among the M. avium subspecies, but only 82.9 and 79.7% identities with the PE and PPE sequences of M. intracellulare, respectively. A detailed analysis of the amino acid sequences was performed between M. avium subsp. paratuberculosis and M. avium subsp. hominissuis. Most differences were detected in the PPE proteins, with amino acid substitutions and frame shifts leading to unique amino acid sequences. In conclusion, several unique PPE proteins were identified in MAC organisms next to numerous polymorphisms in both the PE and PPE gene families. These substantial differences could help explain the divergence in phenotypes within the MAC and could lead to diagnostic tests with better discriminatory abilities.


* Corresponding author. Mailing address: Department of Production Animal Health, Faculty of Veterinary Medicine, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada. Phone: (403) 220-5393. Fax: (403) 210-3939. E-mail: jdebuck{at}ucalgary.ca

{triangledown} Published ahead of print on 14 January 2009.

{dagger} Supplemental material for this article may be found at http://jcm.asm.org/.


Journal of Clinical Microbiology, April 2009, p. 1002-1011, Vol. 47, No. 4
0095-1137/09/$08.00+0     doi:10.1128/JCM.01313-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.