title: Comparative genomics reveal extensive transposon-mediated genomic plasticity and diversity among potential effector proteins within the genus Coxiella.
abstract: 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.
authors.affiliation: Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 S. 4th Street, Hamilton, MT 59840, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Beare
authors.forename: Nathan
authors.initials: N
authors.lastname: Unsworth
authors.forename: Masako
authors.initials: M
authors.lastname: Andoh
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Voth
authors.forename: Anders
authors.initials: A
authors.lastname: Omsland
authors.forename: Stacey D
authors.initials: SD
authors.lastname: Gilk
authors.forename: Kelly P
authors.initials: KP
authors.lastname: Williams
authors.forename: Bruno W
authors.initials: BW
authors.lastname: Sobral
authors.forename: John J
authors.initials: JJ
authors.lastname: Kupko
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Porcella
authors.forename: James E
authors.initials: JE
authors.lastname: Samuel
authors.forename: Robert A
authors.initials: RA
authors.lastname: Heinzen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002874:Chromosome Mapping; D002876:Chromosomes, Bacterial; D016997:Coxiella burnetii / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D004251:DNA Transposable Elements / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D014644:Genetic Variation; D016680:Genome, Bacterial; D023281:Genomics; D010802:Phylogeny; D016415:Sequence Alignment; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D004269:DNA, Bacterial