Human mesenchymal stem cell based intracellular dormancy model of Mycobacterium tuberculosis.
Understanding the biology of the tuberculosis pathogen during dormant asymptomatic infection, called latent tuberculosis is crucial to decipher a resilient therapeutic strategy for the disease. Recent discoveries exhibiting presence of pathogen's DNA and bacilli in mesenchymal stem cells (MSCs) of human and mouse despite completion of antitubercular therapy, indicates that these specific cells could be one of the niches for dormant Mycobacterium tuberculosis in humans. To determine if in vitro infection of human MSCs could recapitulate the in vivo characteristics of dormant M. tuberculosis, we examined survival, phenotype, and drug susceptibility of the pathogen in MSCs. When a very low multiplicity of infection (1:1) was used, M. tuberculosis could survive in human bone marrow derived MSCs for more than 22 days without any growth. At this low level of infection, the pathogen did not cause any noticeable host cell death. During the later phase of infection, MSC-residing M. tuberculosis exhibited increased expression of HspX (a 16-kDa alpha-crystallin homolog) with a concurrent increase in tolerance to the frontline antitubercular drugs Rifampin and isoniazid. These results present a human MSC-based intracelllular model of M. tuberculosis infection to dissect the mechanisms through which the pathogen acquires and maintains dormancy in the host.
['Singh|Vipul K|VK|', 'Mishra|Abhishek|A|', 'Bark|Steven|S|', 'Mani|Arunmani|A|', 'Subbian|Selvakumar|S|', 'Hunter|Robert L|RL|', 'Jagannath|Chinnaswamy|C|', 'Khan|Arshad|A|']
D000818:Animals D000890:Anti-Infective Agents D000942:Antigens, Bacterial D000995:Antitubercular Agents D001426:Bacterial Proteins D001853:Bone Marrow D002470:Cell Survival D004361:Drug Tolerance D054884:Host-Pathogen Interactions D006801:Humans D007538:Isoniazid D055985:Latent Tuberculosis D059630:Mesenchymal Stem Cells D051379:Mice D008826:Microbial Sensitivity Tests D009169:Mycobacterium tuberculosis D010641:Phenotype D012293:Rifampin D014376:Tuberculosis
Mesenchymal stem cells Dormancy Mycobacterium tuberculosis Rifampin Isoniazid Drug tolerance Intracellular infection