Journal
PATHOGENS AND DISEASE
Volume 70, Issue 3, Pages 359-369Publisher
OXFORD UNIV PRESS
DOI: 10.1111/2049-632X.12144
Keywords
Mycobacterium tuberculosis; drug resistant; drug tolerant; biofilm; microbial communities
Categories
Funding
- NIH NIAID [AI083856, 1RO1AI106733, AI070456, 1R01HL090991]
- Science Foundation Arizona
- Rebecca Runyon Bryan Chair for CF, Ira
- Libbie Pink Charitable Fund
Ask authors/readers for more resources
There is an urgent need to improve methods used to screen antituberculosis drugs. An in vitro assay was developed to test drug treatment strategies that specifically target drug-tolerant Mycobacterium tuberculosis. The H37Rv strain of M.tuberculosis survived antimicrobial treatment as attached microbial communities when maintained in tissue culture media (RPMI-1640) with or without lysed human peripheral blood leukocytes. When cultured planktonically in the presence of Tween-80, bacilli failed to form microbial communities or reach logarithmic phase growth yet remained highly susceptible to antimicrobial drugs. In the absence of Tween, bacilli tolerated drug therapy by forming complex microbial communities attached to untreated well surfaces or to the extracellular matrix derived from lysed human leukocytes. Treatment of microbial communities with DNase I or Tween effectively dispersed bacilli and restored drug susceptibility. These data demonstrate that in vitro expression of drug tolerance by M.tuberculosis is linked to the establishment of attached microbial communities and that dispersion of bacilli targeting the extracellular matrix including DNA restores drug susceptibility. Modifications of this in vitro assay may prove beneficial in a high-throughput platform to screen new antituberculosis drugs especially those that target drug-tolerant bacilli.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available