A biosafety level-2 dose-dependent lethal mouse model of spotted fever rickettsiosis: Rickettsia parkeri Atlantic Rainforest-like isolate

Background The species of the Rickettsia genus is separated into four groups: the ancestral group, typhus group, transitional group and spotted fever group. Rickettsia parkeri, a spotted fever group Rickettsia, has been reported across the American continents as infecting several tick species and is associated with a relatively mild human disease characterized by eschar formation at the tick feeding site, fever, myalgia and rash. Currently several mouse models that provide a good approach to study the acute lethal disease caused by Rickettsia, but these models can only be performed in an animal biosafety level 3 laboratory. We present an alternative mouse model for acute lethal rickettsial disease, using R. parkeri and C3H/HeN mice, with the advantage that this model can be studied in an animal biosafety level 2 laboratory. Principal findings In the C3H/HeN mouse model, we determined that infection with 1 × 10⁶ and 1 × 10⁷ viable R. parkeri Atlantic Rainforest-like isolate produced dose-dependent severity, whereas infection with 1 × 10⁸ viable bacteria resulted in a lethal illness. The animals became moribund on day five or six post-infection. The lethal disease was characterized by ruffled fur, erythema, labored breathing, decreased activity, and hunched back, which began on day three post-infection (p.i.) and coincided with the peak bacterial loads. Significant splenomegaly (on days three and five p.i.), neutrophilia (on days three and five p.i.), and thrombocytopenia (on days one, three and five p.i.) were observed. Significance The greatest advantage of this inbred mouse model is the ability to investigate immunity and pathogenesis of rickettsiosis with all the tools available at biosafety level 2. Author summary Rickettsia is a bacterial genus that contains distinct species that are transmitted by arthropods. Many of these agents produce infection and disease in humans. The illness can range from very aggressive, such as Rocky Mountain spotted fever caused by Rickettsia rickettsii, to mild human disease characterized by eschar formation at the tick feeding site and less severe symptoms caused by Rickettsia parkeri. To study these diseases, animal models are invaluable, and mouse models offer the best advantages. Several mouse models are most useful for study of the acute lethal disease produced by these bacteria, providing the opportunity to test different treatments and vaccine candidates. However, work with these models requires an animal biosafety level 3 laboratory. In this report, we present an alternative mouse model to study acute lethal spotted fever group rickettsial disease with the advantage that experiments can be performed at biosafety level 2.