Susceptibility of motile and cystic forms of Borrelia burgdorferi to ranitidine bismuth citrate

Abstract.

Gastrointestinal symptoms accompanying Lyme disease have not been considered in the treatment of Lyme patients yet. Here we examine the effect of ranitidine bismuth citrate (RBC) on motile and cystic forms of Borrelia burgdorferi in vitro, to determine whether it could cure this bacterial infection in the gastrointestinal tract. When motile forms of B. burgdorferi were exposed to RBC for 1 week at 37 °C, the minimal bactericidal concentration (MBC) was >64 mg/ml. At 30 °C, the MBC was >256 mg/ml. When the incubation lasted for 2 weeks at 37 °C, the MBC dropped to >2 mg/ml. Bismuth aggregates were present on the surface of B. burgdorferi when RBC≥MBC, as shown by transmission electron microscopy (TEM). Cystic forms of B. burgdorferi, exposed to RBC for 2 weeks at 37 °C, were examined by cultivation in BSK-H medium (Sigma B3528). They were stained with acridine orange (pH 6.4, pH 7.4) and studied by TEM. The MBC for RBC for young cystic forms (1 day old) and old cysts (8 months old) was estimated to be >0.125 mg/ml and >2 mg/ml, respectively. Bismuth aggregates were attached to the cysts and, in some, the pin-shaped aggregates penetrated the cyst wall. The bismuth aggregates also bound strongly to blebs and granules of B. burgdorferi when RBC≥MBC. When B. burgdorferi is responsible for gastrointestinal symptoms, bismuth compounds may be candidates for eradication of the bacterium from the gastrointestinal tract.