Genome Analysis of Coxiella burnetii Species: Insights into Pathogenesis and Evolution and Implications for Biodefense

Abstract

Coxiella burnetii, the etiological agent of Q fever, is a class B biodefense agent. We are continuing the momentum of discovery generated by the first Coxiella genome sequences by extending the breadth of genomics to include four additional heterogeneous C. burnetii strains. We are also sequencing the genome of Rickettsiella grylli, an intracellular parasite of grasshoppers and the closest known phylogenetic relative to the Coxiella group. These data will enable the investigation of fundamental questions about Coxiella pathogenicity and virulence as well as broader evolutionary questions about the transition to obligate intracellular life. Specifically, sequence comparisons will permit examination of genetic differences, allowing us to address key questions: What core genes are necessary for an obligate intracellular lifestyle and developmental cycle of the genus? What specific genetic determinants can be linked to virulence properties such as host preference, disease severity, and pathology (i.e., acute vs. chronic disease)? What are the frequencies of mutation and intragenomic recombination, and levels of genome reduction? What specific factors are relevant to colonization and virulence in human hosts (based on comparisons with R. grylli)? From a public health and biodefense perspective, exposure to different strains, either natural or due to illegitimate release, may have different outcomes. With extensive genomic-level information from diverse strains, investigators can determine effective drug and vaccine targets and design methods to accurately type Coxiella based on a subset of genes, opening the way for cost-effective targeted PCR- or antibody-based tests.

Molecular detection of Rickettsia, Coxiella and Rickettsiella DNA in three native Australian tick species

“…Several strains of C. burnetii exist, all recognized as a sole species and possessing the same unique genomic characteristics (Seshadri and Samuel 2005;Cutler et al 2006). Related species have been identified within ticks collected from birds (Reeves et al 2005), from the environment (Bernasconi et al 2002;Mediannikov et al 2003;Jasinskas et al 2007) and in association with high mortality in crustaceans (Tan and Owens 2000).…”

A unique Coxiella burnetii lipoprotein involved in metal binding (LimB)

“…BLAST was used to search the GenBank database for similar sequences. Published genomic sequences of six C. burnetii strains (RSA 493, RSA 331, Q177, Q154, Q212 and 5J108-111) (Beare et al, 2009) (Seshadri & Samuel, 2005;Seshadri et al, 2003) possess ORFs that are 100 % identical to CBU1224a. In each strain, the 198 bp ORF is flanked by genes encoding haloalkane dehalogenase (111 bp upstream) and an RmuC family protein (105 bp downstream).…”

“…Second, repeated passage in tissue culture or embryonated hens' eggs results in the spontaneous generation of attenuated 'phase II' (PII) organisms that synthesize a 'rough' LPS that can be caused by a chromosomal deletion (Hoover et al, 2002;Vodkin & Williams, 1986), and may be handled in a BSL-2 laboratory. Finally, a number of C. burnetii strains [such as 'Nine Mile' (NM)] have been isolated from different parts of the world and have been grouped according to their association with acute or chronic disease manifestations of Q fever (Beare et al, 2009;Seshadri & Samuel, 2005).…”

Tripping on Acid: Trans-Kingdom Perspectives on Biological Acids in Immunity and Pathogenesis

“…Finally, C. burnetii encodes an unusually high number of basic proteins. The average pI value for all predicted proteins in the genome of the Nine Mile reference strain is 8.25 [86], [87]; 60% of the proteome is acidic [88]. Moreover, approximately 45% of C. burnetii proteins were found to have a pI value of ≥9, which is higher than the sequenced genomes of other intracellular bacterial pathogens [89].…”