The Impact of Lesion Diversity on Tuberculosis Therapy
Véronique Dartois, Ph.D.
Public Health Research Institute,
NJ Medical School, Rutgers,
The State University of New Jersey
Abstract:
For the successful treatment of pulmonary tuberculosis, drugs need to penetrate complex lung lesions and permeate the mycobacterial cell wall in order to reach their intracellular targets. In addition, TB drugs face a second challenge in these remote niches where various stresses imposed by the immune response and local conditions push M. tuberculosis into a state of dormancy which makes these subpopulations phenotypically tolerant to antibiotic therapy. Anti-tuberculosis drugs were introduced into clinical use without considering the pharmacokinetic and pharmacodynamic properties that influence drug distribution and activity, and this has contributed to the long duration and limited success of current therapies. We have developed methods to quantify and image drug distribution in infected lung tissue, and to measure their potency against M. tuberculosis bacilli residing in necrotic granulomas and cavities. Our results show that different drugs present with very different patterns of partitioning into lung lesion compartments and that intra-caseum M. tuberculosis is significantly more tolerant to antibiotic activity than actively replicating bacteria in a test tube. I will present how these methodologies can be applied to design optimized multidrug regimens.
Biography:
2012–present Associate Professor, Public Health Research Institute, NJ Medical School, Rutgers,
The State University of New Jersey
2005-2012 Executive Director, Pharmacology, Novartis Institute for Tropical Diseases, Singapore
2004 Senior Scientist, Adaptive Therapeutics Inc., San Diego, CA
1997-2003 Principal Scientist, Embiosis Pharmaceuticals, Inc., Carlsbad, CA.
1996-1997 Postdoctoral Fellow, Dept. of Microbial Biochemistry, Pasteur Institute, Paris.
1993-1996 Postdoctoral Fellow, Division of Cell Biology, Scripps Research Institute, La Jolla, CA.
Time: Mar. 14th, 2017, 16:30-17:30 pm
Venue: New Biology Building, Room 143
Host: Dr. Babak Javid
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