Efflux-Mediated Multidrug Tolerance in Replicating Intracellular Mycobacteria
Event details
| Date | 17.06.2011 |
| Hour | 14:00 |
| Speaker | Kristin Adams (University of Washington, Ramakrishnan Laboratory) |
| Location |
SV 1717a
|
| Category | Conferences - Seminars |
Treatment of tuberculosis requires long-term multidrug therapy to
overcome tolerance. Using Mycobacterium marinum-infected zebrafish
larvae for in vivo characterization of antitubercular drug activity and
tolerance, we found that multi-drug tolerant bacteria arise within days
of infection. We identified areas of infection where the bacteria
continued to grow and disseminate, despite overall effective drug
treatment. Using both M. marinum and M. tuberculosis, we found that this
tolerance is also induced upon infection in cultured macrophages and
that these tolerant bacteria are associated with a replicating
intracellular population. Finally, using a combination of bacterial
mutants and pharmacological inhibitors like verapamil, we found that
bacterial efflux pumps required for intracellular growth also mediate
macrophage-induced antibiotic tolerance. The addition of verapamil, or
more specific inhibitors, to standard antitubercular therapy may shorten
the duration of curative treatment.
Adams KN et al. (2011) Drug tolerance in replicating mycobacteria
mediated by a macrophage-induced efflux mechanism. Cell 145(1): 39-53.
Practical information
- General public
- Free
Contact
- Prof John McKinney