This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beare, P. A. Articles by Heinzen, R. A. Search for Related Content PubMed PubMed Citation Articles by Beare, P. A. Articles by Heinzen, R. A.

Genetic Diversity of the Q Fever Agent, Coxiella burnetii, Assessed by Microarray-Based Whole-Genome Comparisons

Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites,¹ Laboratory of Persistent Viral Diseases,³ Genomics Core Facility, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840,⁴ Department of Medical Microbiology and Immunology, Texas A&M University System, Health Science Center, College Station, Texas 77843²

Received 19 September 2005/ Accepted 15 December 2005

Coxiella burnetii, a gram-negative obligate intracellular bacterium, causes human Q fever and is considered a potential agent of bioterrorism. Distinct genomic groups of C. burnetii are revealed by restriction fragment-length polymorphisms (RFLP). Here we comprehensively define the genetic diversity of C. burnetii by hybridizing the genomes of 20 RFLP-grouped and four ungrouped isolates from disparate sources to a high-density custom Affymetrix GeneChip containing all open reading frames (ORFs) of the Nine Mile phase I (NMI) reference isolate. We confirmed the relatedness of RFLP-grouped isolates and showed that two ungrouped isolates represent distinct genomic groups. Isolates contained up to 20 genomic polymorphisms consisting of 1 to 18 ORFs each. These were mostly complete ORF deletions, although partial deletions, point mutations, and insertions were also identified. A total of 139 chromosomal and plasmid ORFs were polymorphic among all C. burnetii isolates, representing ca. 7% of the NMI coding capacity. Approximately 67% of all deleted ORFs were hypothetical, while 9% were annotated in NMI as nonfunctional (e.g., frameshifted). The remaining deleted ORFs were associated with diverse cellular functions. The only deletions associated with isogenic NMI variants of attenuated virulence were previously described large deletions containing genes involved in lipopolysaccharide (LPS) biosynthesis, suggesting that these polymorphisms alone are responsible for the lower virulence of these variants. Interestingly, a variant of the Australia QD isolate producing truncated LPS had no detectable deletions, indicating LPS truncation can occur via small genetic changes. Our results provide new insight into the genetic diversity and virulence potential of Coxiella species.

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

This article has been cited by other articles:

• Omsland, A., Cockrell, D. C., Fischer, E. R., Heinzen, R. A. (2008). Sustained Axenic Metabolic Activity by the Obligate Intracellular Bacterium Coxiella burnetii. J. Bacteriol. 190: 3203-3212 [Abstract] [Full Text]  
• Woc-Colburn, A. M., Garner, M. M., Bradway, D., West, G., D'Agostino, J., Trupkiewicz, J., Barr, B., Anderson, S. E., Rurangirwa, F. R., Nordhausen, R. W. (2008). Fatal Coxiellosis in Swainson's Blue Mountain Rainbow Lorikeets (Trichoglossus haematodus moluccanus). Vet Pathol 45: 247-254 [Abstract] [Full Text]  
• Greenberg, D. E., Porcella, S. F., Zelazny, A. M., Virtaneva, K., Sturdevant, D. E., Kupko, J. J. III, Barbian, K. D., Babar, A., Dorward, D. W., Holland, S. M. (2007). Genome Sequence Analysis of the Emerging Human Pathogenic Acetic Acid Bacterium Granulibacter bethesdensis. J. Bacteriol. 189: 8727-8736 [Abstract] [Full Text]  
• Raghavan, R., Miller, S. R., Hicks, L. D., Minnick, M. F. (2007). The Unusual 23S rRNA Gene of Coxiella burnetii: Two Self-Splicing Group I Introns Flank a 34-Base-Pair Exon, and One Element Lacks the Canonical {Omega}G. J. Bacteriol. 189: 6572-6579 [Abstract] [Full Text]  
• Voth, D. E., Howe, D., Heinzen, R. A. (2007). Coxiella burnetii Inhibits Apoptosis in Human THP-1 Cells and Monkey Primary Alveolar Macrophages. Infect. Immun. 75: 4263-4271 [Abstract] [Full Text]  
• Beare, P. A., Howe, D., Cockrell, D. C., Heinzen, R. A. (2007). Efficient Method of Cloning the Obligate Intracellular Bacterium Coxiella burnetii. Appl. Environ. Microbiol. 73: 4048-4054 [Abstract] [Full Text]  
• Lloyd, A. L., Rasko, D. A., Mobley, H. L. T. (2007). Defining Genomic Islands and Uropathogen-Specific Genes in Uropathogenic Escherichia coli. J. Bacteriol. 189: 3532-3546 [Abstract] [Full Text]  
• Coleman, S. A., Fischer, E. R., Cockrell, D. C., Voth, D. E., Howe, D., Mead, D. J., Samuel, J. E., Heinzen, R. A. (2007). Proteome and Antigen Profiling of Coxiella burnetii Developmental Forms. Infect. Immun. 75: 290-298 [Abstract] [Full Text]