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

Abstract

12 13 Background 14 15The species of the Rickettsia genus is separated into four groups: the ancestral group, 16 typhus group, transitional group and spotted fever group. Rickettsia parkeri, a spotted 17 fever group Rickettsia, has been reported across the American continents as infecting 18 several tick species and is associated with a relatively mild human disease characterized 19 by eschar formation at the tick feeding site, fever, myalgia and rash. Currently several 20 mouse models that provide a good approach to study the acute lethal disease caused by 21 Rickettsia, but these models can only be performed in an animal biosafety level 3 22 laboratory. We present an alternative mouse model for acute lethal rickettsial disease, 2 23 using R. parkeri and C3H/HeN mice, with the advantage that this model can be studied 24 in an animal biosafety level 2 laboratory. 25 26 Principal findings 27 28 In the C3H/HeN mouse model, we determined that infection with 1x10 6 and 1x10 7 viable 29 R. parkeri Atlantic Rainforest-like isolate produced dose-dependent severity, whereas 30 infection with 1x10 8 viable bacteria resulted in a lethal illness. The animals became 31 moribund on day five or six post-infection. The lethal disease was characterized by ruffled 32 fur, erythema, labored breathing, decreased activity, and hunched back, which began on 33 day three post-infection (p.i.) and coincided with the peak bacterial loads. Significant 34 splenomegaly (on days three and five p.i.), neutrophilia (on days three and five p.i.), and 35 thrombocytopenia (on days one, three and five p.i.) were observed. 36 37 Significance 38 39The greatest advantage of this inbred mouse model is the ability to investigate immunity 40 and pathogenesis of rickettsiosis with all the tools available at biosafety level 2. 41 42 Author summary 43 44Rickettsia is a bacterial genus that contains distinct species that are transmitted by 45 arthropods. Many of these agents produce infection and disease in humans. The illness 3 46 can range from very aggressive, such as Rocky Mountain spotted fever caused by 47 Rickettsia rickettsii, to mild human disease characterized by eschar formation at the tick 48 feeding site and less severe symptoms caused by Rickettsia parkeri. To study these 49 diseases, animal models are invaluable, and mouse models offer the best advantages. 50Several mouse models are most useful for study of the acute lethal disease produced by 51 these bacteria, providing the opportunity to test different treatments and vaccine 52 candidates. However, work with these models requires an animal biosafety level 3 53 laboratory. In this report, we present an alternative mouse model to study acute lethal 54 spotted fever group rickettsial disease with the advantage that experiments can be 55 performed at biosafety level 2. 56 57 63 64 Rickettsia parkeri, a member of the SFG, has been reported across the American 65 continents as infecting several tick species including the Amblyomma maculatum 66 complex (A. maculatum, A. triste, A. tig...