The principal obstacle to successful treatment of tuberculosis is the lengthy duration of current regimens, which require administration of multiple drugs for 6-9 months. The requirement for prolonged therapy is attributed to sub-populations of bacillary "persisters" that are refractory to antimicrobials. The persisters are not drug-resistant in the conventional (heritable) sense and it is a mystery why they are spared whilst their genetically identical siblings are killed. The third part of this lecture describes recent work in our laboratory using microfluidics and time-lapse microscopy to analyze the behavior of drug-stressed bacteria at single-cell resolution. These studies challenge conventional views of how antimicrobials kill (or fail to kill) bacteria.
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