The pregnane X receptor in tuberculosis therapeutics.

INTRODUCTION: Among the infectious diseases, tuberculosis (TB) remains the second most common cause of death after HIV. TB treatment requires the combination of multiple drugs including the rifamycin class. However, rifamycins are activators of human pregnane X receptor (PXR), a transcription factor that regulates drug metabolism, drug resistance, energy metabolism and immune response. Rifamycin-mediated PXR activation may affect the outcome of TB therapy. AREAS COVERED: This review describes the role of PXR in modulating metabolism, efficacy, toxicity and resistance to anti-TB drugs; as well as polymorphisms of PXR that potentially affect TB susceptibility. EXPERT OPINION: The wide range of PXR functions that mediate drug metabolism and toxicity in TB therapy are often underappreciated and thus understudied. Further studies are needed to determine the overall impact of PXR activation on the outcome of TB therapy.