In a latest study by Dr. Bikul Das, (he discovered altruism in embryonic stem cells and their link to cancer) and team, the tuberculosis bacteria, Mycobacterium tuberculosis, have been found to infiltrate and settle down in the mesenchymal stem cells found in the bone marrow, and remaining dormant for many years after treatment of the disease with antibiotics. The scientists were able to isolate genetic material from bacteria inside the cells as well as isolate viable/active bacteria from cells of patients who had undergone extensive treatment for the disease.
I observed the TB bacteria inside bone marrow cells about 15 years ago while doing clinical practice in India. So, it is a nice feeling to confirm the findings now!
says Dr. Das in an email.
Dr. Bikul Das’ 15 Years Journey In the Pursuit Of the Elusive TB Bacteria
- Dr. Das first noticed tuberculosis bacteria in bone marrow biopsies of patients fifteen years ago.
- This observation piqued his interest and gave him the idea that the bacteria could be infiltrating the cells.
- As a postdoctoral fellow at Stanford, Dr. Das exposed bone marrow stem cells from healthy human donors to tuberculosis bacteria.
- He found that the bacteria invaded bone marrow cells and remained viable inside cells for up to 2 weeks (in-vitro)
- The bacteria seemed to prefer mesenchymal cells exhibiting CD271 cell surface marker.
- Another observation was that if stem cells were initiated to differentiate, bacteria presented decreasing viability.
- Dr. Das investigated his observations on a mouse model:
- A genetically modified strain of tuberculosis bacteria was made that replicated only in presence of streptomycin
- In the absence of streptomycin, bacteria were dormant in the mouse
- Lab mice were exposed to aerosolized modified bacteria
- Naturally, mice were infected
- Dormant bacteria were found in mesenchymal stem cells in bone marrow after six months of streptomycin withdrawal.
- Stem cells carrying dormant bacteria were injected into healthy mice
- These mice developed symptoms of tuberculosis – granulomas (lung lesions)
- Dr. Das tested the mouse model results in a clinical study conducted in India.
- Bone marrow biopsies from 9 people who had undergone complete antibiotic treatment and whose sputum did not have any detectable bacteria were collected
- Researchers were able to detect bacterial DNA in mesenchymal stem cells from bone marrow in 8 of the 9 people
- Live bacteria was isolated from stem cells of 2 of the 8 people
So, what’s the good news?
A new possible target in the fight against tuberculosis which infects 2.2 billion people worldwide, since now we know how the disease remains dormant in healthy individuals, previously treated for TB and how a re-infection may occur.
Mesenchymal stem cells migrate to injury or inflammation sites of the body and begin dividing here. Migrating cells can easily reactivate the disease in the lungs.
Dr. Das and his team have often observed tubercular relapse in COPD (chronic obstructive pulmonary disease) patients and Dr. Das suggests that this co-relation between COPD and tubercle relapse could be due to migrating bacteria carrying mesenchymal cells reactivating tuberculosis infection.
The study was published in the journal, Science Translational Medicine. Dr. Das is the lead author, with Dr. Flesher as the co-senior author of the study. The research was conducted in collaboration with research teams at Forsyth Institute in Cambridge, Massachusetts, the Hospital for Sick Children in Toronto, and research groups in India.
The study definitely opens up new avenues for investigating TB bacteria on the lines of a complete cure!
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