Method to kill dormant TB bacteria
Researchers have found that inhibiting lipid synthesis inside stem cells can help in killing TB bacteria that are found inside the stem cells in a dormant state.
TB bacteria inside the macrophages actively divide whereas microbes inside stem cells lie dormant and also make the stem cells less likely to replicate thus surviving for an extended period of time.
Research showed that the two cells are programmed very differently to support active and dormant TB bacteria infection.
TB bacteria are free in the intracellular fluid (cytosol) of the mesenchymal stem cells while they are surrounded by the macrophage cell membrane on being engulfed.
This allows the bacteria to promote rapid synthesis of lipids inside the stem cells and hide within the lipid droplets so created.
Studies using human mesenchymal stem cells and macrophages and mice model studies helped to understand how TB bacteria hijack the cellular mechanism to stop the stem cells from replicating and turn themselves dormant.
The bacteria instruct the stem cells to synthesise lipids and hide inside them. The stem cells don’t kill microbes that are inside lipid droplets.
When inhibitors to block lipid synthesis were used, there was reduced expression of genes that regulate dormancy of TB bacteria and replication of stem cells.
This helped confirm that TB bacteria induce lipid synthesis in stem cells and hide inside the lipid cells to escape from anti-TB drugs.
Killing the bacteria and preventing disease reactivation can be achieved by inducing autophagy (mechanism by which cells removes unnecessary or dysfunctional components) along with anti-TB drugs.
Inducing autophagy led to elimination of TB bacteria from stem cells. Addition of autophagy-inducing drug along with isoniazid led to sterile cure of TB and prevention of disease reactivation.