Gene signatures of rifampin, rifabutin an rifapentine anti-tuberculosis drugs in human primary hepatocytes.

We report the application of next generation sequencing technology for high-throughput profiling of total RNA to determine the expression of all genes expressed in human primary hepatocytes derived from three healthy (drug/tobacco/alcohol free) volunteers in response to anti-tuberculosis antibiotics, including, rifampin, rifabutin and rifapentine through comparison with gene profiles of vehicle (methanol) treated and untreated cells. We determined the response of over 22,000 genes expressed in human primary hepatocytes following rifampin, rifabutin and rifapentine treatment for 72h. We found that several drug metabolizing enzymes, including cytochrome P450 3A4 and drug transporters are differentially expressed in human primary hepatocytes in response to rifamycin antibiotics. We utilized the information generated with differential gene expression study to determine interaction of rifamyicn antibiotics with antiviral, antibacterial, antifungal agents and other drugs used to treat several ailments in tuberculosis patients. This study provides a comprehensive profiles of genes expressed in response to rifamycin antibiotics towards characterization of their drug interactions with the drugs that are combined to treat various viral, bacterial, fungal and other diseases, including cancer. Overall design: Profiling the genes expressed in human primary hepatocytes in response to rifampin, rifabutin and rifapentine anti-tuberculosis antibiotics.