Chlamydia trachomatis is an obligate intracellular bacterial pathogen responsible for the most common bacterial sexually transmitted infection (STI) worldwide and is a leading cause of preventable blindness in developing countries. The bacterium represents an ideal candidate for drug repurposing efforts due to its complex developmental cycle and increasing antibiotic resistance profiles. Clofazimine is an antibiotic compound that has been primarily used for the treatment of leprosy and has been studied to combat multi-drug-resistant tuberculosis. However, long-term use of oral clofazimine can result in toxicity. We hypothesize that taurine, a semi-essential amino acid in mammalian tissue, can negate the negative cytotoxic effects of clofazimine, adding to the arsenal to combat C. trachomatis.  

To determine the optimal concentration and measure toxicity, we have treated human microglial macrophages with increasing concentrations (25 – 1500ug/ml) of clofazimine and determined cytotoxicity qualitatively (light microscopy) and quantitatively (LDH assay). The data shows that concentrations greater than 500ug/ml result in significant cell lysis as early as 6h post-treatment. At concentrations below 100ug/ml cells survived and proliferated beyond 3 days. An important finding in this study was to solubilize clofazimine without recrystallization in infection media over time. Deposition of clofazimine crystals in pulmonary macrophages can lead to clinically significant crystal deposition syndrome with cough and dyspnea. Ongoing studies seek to determine the optimal dose of taurine needed to mitigate the cytotoxic effects of clofazimine at various concentrations and the combined effect on chlamydial infection in vitro.