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Coxiella burnetii Genome Project

Goals

The goal of this project is to generate complete genome sequence data from four Coxiella burnetii isolates and Rickettsiella grylli in order to define variations in strains that are responsible for differences in virulence and host range. Additionally, comparative genomics of a newly-discovered Coxiella sp. of ticks and Coxiella burnetii will be done. The goals of the comparative genomics project are to characterize a core set of proteins for Coxiella spp. and to identify genes unique to C. burnetii that could facilitate this pathogen's transmission to or virulence in vertebrates.

Rationale

Q fever is a Category B select agent and has long been considered of high potential as an agent for biological warfare or terrorism [2]. Although infection mortality is low and secondary transmission between humans is rare, the acute illnesses frequently incapacitate infected individuals, and the attack rate can be high after point-source exposures [3, 4]. Moreover, in some cases acute illness is followed by chronic infection, such as "culture-negative" endocarditis [3], or by a disabling post-infection fatigue syndrome [5]. Besides natural cycles of C. burnetii among wildlife and their tick vectors, the disease is enzootic and endemic in many regions of the world with cattle, goat, and sheep raising. The high concentrations of infectious microorganisms in placentas, milk, vaginal secretions, and feces of infected animals provide a ready, "low-tech" source of an infectious agent for would-be terrorists. Excreted organisms are highly resistant to drying, and the minimum inoculum for infection by the aerosol route is low. There have been several outbreaks of disease from point-source exposures through inadvertent aerosols, so sophisticated "weaponization" is not a requirement for successful delivery of this agent. Ampicillin-resistant C. burnetii have been obtained through genetic transformation with C. burnetii-E. coli shuttle plasmids [5], so engineering for resistance to commonly recommended antibiotics, such as tetracyclines, is feasible.

Strain Selection

Diverse geographical distribution of C. burnetii has resulted in the accumulation of varied isolates that appear to be serologically similar. Isolates from mammalian and arthropod hosts have been differentiated based on genetic and phenotypic differences into at least 6 different genomic groups [26-29]. We propose to have a representative strain from each genomic group sequenced. The strains selected constitute a selection based on the virulence potential, disease phenotypes, host organism, geographical distribution, and gross genomic distinctions.

Investigators and Collaborators

Heidelberg, John

University of Southern California

Madupu, Ramana

J. Craig Venter Institute

Myers, Garry

Institute for Genome Sciences, University of Maryland School of Medicine

Samuel, James

Texas A&M Health Science Center

 
 
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