Genome Analysis ofCoxiella burnetiiSpecies: Insights into Pathogenesis and Evolution and Implications for Biodefense

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Abstract
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 firstCoxiellagenome sequences by extending the breadth of genomics to include four additional heterogeneousC. burnetiistrains. We are also sequencing the genome ofRickettsiella grylli, an intracellular parasite of grasshoppers and the closest known phylogenetic relative to theCoxiellagroup. These data will enable the investigation of fundamental questions aboutCoxiellapathogenicity 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 withR. 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 typeCoxiellabased on a subset of genes, opening the way for cost‐effective targeted PCR‐ or antibody‐based tests.