title: The SCID Mouse Model for Identifying Virulence Determinants inCoxiella burnetii.
abstract: Coxiella burnetiiis an intracellular, zoonotic pathogen that is the causative agent of Q fever. Infection most frequently occurs after inhalation of contaminated aerosols, which can lead to acute, self-limiting febrile illness or more serve chronic infections such as hepatitis or endocarditis. Macrophages are the principal target cells during infection whereC. burnetiiresides and replicates within a unique phagolysosome-like compartment, theCoxiella-containing vacuole (CCV). The first virulence determinant described as necessary for infection was full-length lipopolysaccarride (LPS); spontaneous rough mutants (phase II) arise after passage in immuno-incompetent hosts. Phase IIC. burnetiiare attenuated in immuno-competent animals, but are fully capable of infecting a variety of host cellsin vitro. A clonal strain of the Nine Mile isolate (RSA439, clone 4), has a 26 KDa chromosomal deletion that includes LPS biosynthetic genes and is uniquely approved for use in BL2/ABL2 conditions. With the advances of axenic media and genetic tools forC. burnetiiresearch, the characterization of novel virulence determinants is ongoing and almost exclusively performed using this attenuated clone. A major problem with predicting essential virulence loci with RSA439 is that, although some cell-autonomous phenotypes can be assessed in tissue culture, no animal model for assessing pathogenesis has been defined. Here we describe the use of SCID mice for predicting virulence factors ofC. burnetii, in either independent or competitive infections. We propose that this model allows for the identification of mutations that are competent for intracellular replicationin vitro, but attenuated for growthin vivoand predict essential innate immune responses modulated by the pathogen during infection as a central pathogenic strategy.
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Bryan, TX, USA.
authors.forename: Erin J
authors.initials: EJ
authors.lastname: van Schaik
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Bryan, TX, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Case
authors.affiliation: Centre National de la Recherche Scientifique, Formation de Recherche en Évolution 3689, Centre d'études d'agents Pathogènes et Biotechnologies Pour la Santé, Université Montpellier Montpellier, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Martinez
authors.affiliation: Centre National de la Recherche Scientifique, Formation de Recherche en Évolution 3689, Centre d'études d'agents Pathogènes et Biotechnologies Pour la Santé, Université Montpellier Montpellier, France.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonazzi
authors.affiliation: Department of Microbial Pathogenesis and Immunology, College of Medicine, Texas A&M University Bryan, TX, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Samuel
mesh_terms: D000818:Animals; D016997:Coxiella burnetii / Q000472:pathogenicity*; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D051379:Mice; D016513:Mice, SCID; D011778:Q Fever / Q000382:microbiology* / Q000473:pathology*; D014774:Virulence; D037521:Virulence Factors / Q000032:analysis*
chemical_list: D037521:Virulence Factors
keywords: C. burnetii; SCID mouse; animal model; transposon mutagenesis; virulence