Tissue Distribution of Doxycycline in Animal Models of Tuberculosis
Martin Gengenbacher, Matthew Zimmerman, Jansy P. Sarathy, Firat Kaya, Han Wang, Marizel Mina, Claire Carter, Md Amir Hossen, Hongwei Su, Carolina Trujillo, Sabine Ehrt, Dirk Schnappinger, Véronique Dartois
Abstract
Doxycycline, an FDA-approved tetracycline, is used in tuberculosis in vivo models for the temporal control of mycobacterial gene expression. In these models, animals are infected with recombinant Mycobacterium tuberculosis carrying genes of interest under transcriptional control of the doxycycline-responsive TetR- tetO unit. To minimize fluctuations of plasma levels, doxycycline is usually administered in the diet. However, tissue penetration studies to identify the minimum doxycycline content in food achieving complete repression of TetR-controlled genes in tuberculosis (TB)-infected organs and lesions have not been conducted.