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

Abstract

Background The species of the Rickettsia genus are 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, regional lymphadenopathy, fever, myalgia and rash. Currently, there are several mouse models that provide good approaches 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 Atlantic Rainforest strain 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 1x10 6 and 1x10 7 viable R . parkeri Atlantic Rainforest strain organisms produced dose-dependent severity, whereas infection with 1x10 8 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 posture, 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 Since R . parkeri is used at biosafety level 2, 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.

Endothelial exosome plays functional role during rickettsial infection

“…R. australis (Cutlack strain) (87) and R. australis (Atlantic rainforest strain)(114) were prepared as described. Uninfected Vero cells were processed as mock control material using the same procedure.…”

Rickettsia parkeri strain Atlantic rainforest in ticks (Acari: Ixodidae) of wild birds in Arauca, Orinoquia region of Colombia

“…R. rickettsii is the causal agent of Rocky Mountain spotted fever (RMSF), Brazilian spotted fever, or Tobia fever in Colombia ( Labruna et al, 2011 ; Oteo et al, 2014 ). Moreover, there are two strains of R. parkeri known to cause rickettsiosis, namely R. parkeri sensu stricto and R. parkeri strain Atlantic rainforest ( Londoño et al, 2019 ). Like in other spotted fever group (SFG) rickettsiae, R. parkeri is transovarially (from female to eggs) and transestadially (from one life history stage to the next) transmitted to ticks.…”

“…Using genetic evidence, Nieri-Bastos et al (2018) , defined that Atlantic rainforest is R. parkeri strain found in the southern part of South America that is transmitted by ticks of the A. ovale complex (i.e., A. ovale and Amblyomma aureolatum ). Other tick species of the Amblyomma maculatum complex ( A. maculatum, Amblyomma triste , and Amblyomma tigrinum ), A. nodosum , Amblyomma parvitarsum and Dermacentor parumapertus have been involved in the transmission of R. parkeri in America ( Paddock et al, 2004 , 2017 ; Nieri-Bastos et al, 2018 ; Londoño et al, 2019 ).…”

Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis

“…C57BL/6 mice have also been proposed as models for R. parkeri upon intravenous (i.v.) delivery of 10 8 bacteria 16 . However, this dose is substantially higher than the number of R. parkeri found in tick saliva or tick salivary glands 17 , and considerable effort is required to generate and concentrate this number of bacteria.…”