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SUMMARY:Efflux-Mediated Multidrug Tolerance in Replicating Intracellular M
 ycobacteria 
DTSTART:20110617T140000
DTSTAMP:20260408T085705Z
UID:94b9d675d19836b77805e181adde972801dcc0fed02e7a9e01fb9f63
CATEGORIES:Conferences - Seminars
DESCRIPTION:Kristin Adams (University of Washington\, Ramakrishnan Laborat
 ory)\nTreatment of tuberculosis requires long-term multidrug therapy to \n
 overcome tolerance. Using Mycobacterium marinum-infected zebrafish \nlarva
 e for in vivo characterization of antitubercular drug activity and \ntoler
 ance\, we found that multi-drug tolerant bacteria arise within days \nof i
 nfection. We identified areas of infection where the bacteria \ncontinued 
 to grow and disseminate\, despite overall effective drug \ntreatment. Usin
 g both M. marinum and M. tuberculosis\, we found that this \ntolerance is 
 also induced upon infection in cultured macrophages and \nthat these toler
 ant bacteria are associated with a replicating \nintracellular population.
  Finally\, using a combination of bacterial \nmutants and pharmacological 
 inhibitors like verapamil\, we found that \nbacterial efflux pumps require
 d for intracellular growth also mediate \nmacrophage-induced antibiotic to
 lerance. The addition of verapamil\, or \nmore specific inhibitors\, to st
 andard antitubercular therapy may shorten \nthe duration of curative treat
 ment.\nAdams KN et al. (2011) Drug tolerance in replicating mycobacteria \
 nmediated by a macrophage-induced efflux mechanism. Cell 145(1): 39-53.
LOCATION:SV 1717a
STATUS:CONFIRMED
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