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Journal of Bacteriology, January 2006, p. 711-723, Vol. 188, No. 2
0021-9193/06/$08.00+0     doi:10.1128/JB.188.2.711-723.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Whole-Genome Plasticity among Mycobacterium avium Subspecies: Insights from Comparative Genomic Hybridizations{dagger}

Chia-wei Wu,1 Jeremy Glasner,1 Michael Collins,2 Saleh Naser,3 and Adel M. Talaat1*

Departments of Animal Health and Biomedical Sciences,1 Pathobiological Sciences, University of Wisconsin—Madison, 1656 Linden Drive, Madison, Wisconsin 53706,2 Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida3

Received 26 August 2005/ Accepted 20 October 2005

Infection with Mycobacterium avium subsp. paratuberculosis causes Johne's disease in cattle and is also implicated in cases of Crohn's disease in humans. Another closely related strain, M. avium subsp. avium, is a health problem for immunocompromised patients. To understand the molecular pathogenesis of M. avium subspecies, we analyzed the genome contents of isolates collected from humans and domesticated or wildlife animals. Comparative genomic hybridizations indicated distinct lineages for each subspecies where the closest genomic relatedness existed between M. avium subsp. paratuberculosis isolates collected from human and clinical cow samples. Genomic islands (n = 24) comprising 846 kb were present in the reference M. avium subsp. avium strain but absent from 95% of M. avium subsp. paratuberculosis isolates. Additional analysis identified a group of 18 M. avium subsp. paratuberculosis-associated islands comprising 240 kb that were absent from most of the M. avium subsp. avium isolates. Sequence analysis of DNA regions flanking the genomic islands identified three large inversions in addition to several small inversions that could play a role in regulation of gene expression. Analysis of genes encoded in the genomic islands reveals factors that are probably important for various mechanisms of virulence. Overall, M. avium subsp. avium isolates displayed a higher level of genomic diversity than M. avium subsp. paratuberculosis isolates. Among M. avium subsp. paratuberculosis isolates, those from wildlife animals displayed the highest level of genomic rearrangements that were not observed in other isolates. The presented findings will affect the future design of diagnostics and vaccines for Johne's and Crohn's diseases and provide a model for genomic analysis of closely related bacteria.

* Corresponding author. Mailing address: Department of Animal Health and Biomedical Sciences, University of Wisconsin—Madison, 1656 Linden Drive, Madison, WI 53706-1581. Phone: (608) 262-2861. Fax: (608) 262-7420. E-mail: atalaat{at}wisc.edu.

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

Journal of Bacteriology, January 2006, p. 711-723, Vol. 188, No. 2
0021-9193/06/$08.00+0     doi:10.1128/JB.188.2.711-723.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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