Fig 1. Effect of FGFR/HSPG inhibition on rickettsial internalization in vitro and in vivo.

(A): ECs were incubated with heparinase (1U/ml), FGFR inhibitor AZD4547 (100 nM), or the vehicle alone (mock-treated) for 1 hour prior to infection with R. rickettsii. At 6 hours post-infection, total DNA was extracted and rickettsial copy number was determined using a standard curve. The asterisks represent a significant change (p ≤ 0.001) compared to mock treatment and the data represent mean ± Standard Error (SE) from a minimum of three independent experiments. (B): AZD4547 was dissolved in a vehicle containing DMSO and 1% (v/v) Tween-80 and orally administered (25 mg/kg/day) to 6–8 weeks old C3H/HeN mice infected with R. conorii (2.25×10⁵ pfu). The control group of animals (infected but mock-treated) received injection of R. conorii and vehicle (DMSO + Tween-80). Mice were euthanized on day 3 post-infection and rickettsial copy number was determined using DNA from the lungs. The data are presented as the mean ± SE of three independent observations.