Evaluation of killing kinetics of anti-tuberculosis drugs on Mycobacterium tuberculosis using a bacteriophage-based assay.
BACKGROUND
Killing kinetics studies on Mycobacterium tuberculosis are labour intensive and time consuming since it takes nearly 6-7 weeks to get the data from an experiment. A modified protocol is required to increase the throughput and expedite the results.


METHODS
The killing kinetics of frontline drugs used for the treatment of tuberculosis was studied using 24-well plates and 2 methods of enumeration of survivors of M. tuberculosis following drug exposure, namely conventional plating (CFU) and a phage-based assay (plaque-forming units) using mycobacteriophage D29.


RESULTS
The use of 24-well plates enabled in reducing the volume of the compound required for the studies and the phage-based enumeration speeded up the readout and compared well with the CFU-based enumeration.


CONCLUSIONS
These results were in agreement with the earlier findings reported with respect to rifampicin, isoniazid and moxifloxacin. Also, this study shows for the first time the concentration-dependent killing of streptomycin, the time-dependent killing of ethambutol and the profiling of an experimental anti-mycobacterial compound by these 2 methods.
Marcel
Nimi
N
AstraZeneca India Private Limited, Bangalore, India.
Nahta
Ajay
A
Balganesh
Meenakshi
M
D000995:Antitubercular Agents / Q000494:pharmacology*; D001435:Bacteriophages / Q000502:physiology*; D007700:Kinetics; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000821:virology*
D000995:Antitubercular Agents