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Infection and Immunity, February 2009, p. 642-656, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01141-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Comparative Genomics Reveal Extensive Transposon-Mediated Genomic Plasticity and Diversity among Potential Effector Proteins within the Genus Coxiella ^,

Paul A. Beare,¹ Nathan Unsworth,² Masako Andoh,² Daniel E. Voth,¹ Anders Omsland,¹ Stacey D. Gilk,¹ Kelly P. Williams,⁴ Bruno W. Sobral,⁴ John J. Kupko III,³ Stephen F. Porcella,³ James E. Samuel,² and Robert A. Heinzen^1*

Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites,¹ Genomics Core Facility, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840,³ Department of Medical Microbiology and Immunology, Texas A&M Health Science Center, College Station, Texas 77843,² Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061⁴

Received 14 September 2008/ Returned for modification 21 October 2008/ Accepted 22 November 2008

Genetically distinct isolates of Coxiella burnetii, the cause of human Q fever, display different phenotypes with respect to in vitro infectivity/cytopathology and pathogenicity for laboratory animals. Moreover, correlations between C. burnetii genomic groups and human disease presentation (acute versus chronic) have been described, suggesting that isolates have distinct virulence characteristics. To provide a more-complete understanding of C. burnetii's genetic diversity, evolution, and pathogenic potential, we deciphered the whole-genome sequences of the K (Q154) and G (Q212) human chronic endocarditis isolates and the naturally attenuated Dugway (5J108-111) rodent isolate. Cross-genome comparisons that included the previously sequenced Nine Mile (NM) reference isolate (RSA493) revealed both novel gene content and disparate collections of pseudogenes that may contribute to isolate virulence and other phenotypes. While C. burnetii genomes are highly syntenous, recombination between abundant insertion sequence (IS) elements has resulted in genome plasticity manifested as chromosomal rearrangement of syntenic blocks and DNA insertions/deletions. The numerous IS elements, genomic rearrangements, and pseudogenes of C. burnetii isolates are consistent with genome structures of other bacterial pathogens that have recently emerged from nonpathogens with expanded niches. The observation that the attenuated Dugway isolate has the largest genome with the fewest pseudogenes and IS elements suggests that this isolate's lineage is at an earlier stage of pathoadaptation than the NM, K, and G lineages.

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* Corresponding author. Mailing Address: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 S. 4th Street, Hamilton, MT 59840. Phone: (406) 375-9695. Fax: (406) 375-9380. E-mail: rheinzen{at}niaid.nih.gov

Published ahead of print on 1 December 2008.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Camilli

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Infection and Immunity, February 2009, p. 642-656, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01141-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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• Raghavan, R., Hicks, L. D., Minnick, M. F. (2009). A Unique Group I Intron in Coxiella burnetii Is a Natural Splice Mutant. J. Bacteriol. 191: 4044-4046 [Abstract] [Full Text]