Introduction: What they say:
A study from the Singapore Immunology Network, Agency for Science, Technology and Research, Singapore; and Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore shows that “Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis.” This study was published, in the 24 March 2017 issue of the Science Family of Journals “Science Immunology,” by Prof. Amit Singhal, Catherine Y. Cheng, and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Probiotic-based therapy for tuberculosis: Probiotic Lactobacillus gasseri SBT2055 deacetylates RelA/p65, inhibits inflammatory gene expression downstream of RelA/p65, inhibits TB pathogenesis, increases the efficacy of anti-TB drug, and promotes M. tuberculosis clearance via upregulation of its target gene
What is known?
Prof. Amit Singhal’s research team has recently shown that: (1) Mycobacterium tuberculosis (Mtb) inhibits Sirtuin-1 (SIRT1) expression, while its activation inhibits the growth of drug-susceptible/resistant strains of Mtb; (2) Myeloid cell–specific SIRT1 deficient mice are more susceptible to Mycobacterium tuberculosis-mediated infection; (3) Sirtuin-1 activators deacetylate RelA/p65 and inhibit the expression of its downstream target (inflammatory) genes; and (4) Sirtuin-1 activators improve lung pathology, inhibit chronic-inflammatory responses and augment efficacy of anti-TB drugs in Mtb-infected mice, suggesting that Sirtuin-1 activators may be used to increase the efficacy of anti-TB drugs.
From Significance of the study to Public health relevance:
Given that: (1) nearly 2.5 billion people out of 7.4 billion total world population are infected with M. tuberculosis; (2) majority of population in Asian and African countries test positive in tuberculin tests; (3) molecular pathways involved and the mechanism of development of drug-resistant tuberculosis is far from understood; (4) treating drug-resistant tuberculosis is still a daunting task; (5) tuberculosis is the second-leading cause of death–first being the HIV–due to an infectious disease; (6) in 2010, out of the 88 lakhs patients test positive for TB, 14.5 lakhs patients died; (7) billions of dollars are being spent each year globally for the treatment of tuberculosis; and (8) most of the TB cases are registered in developing countries—that cannot afford high-cost required for the treatment of drug-resistant TB—compared to developed countries, there is an urgent need to find: (i) a way to inhibit drug-resistant tuberculosis; (ii) a cheaper alternative to the existing expensive drugs; and (iii) a side-effect-free-Natural product-based drug that prevents relapse/recurrence of drug-resistant TB.
From research findings to Therapeutic opportunity:
Probiotic Lactobacillus gasseri SBT2055, by decreasing the expression of its target gene, it may: (1) deacetylate RelA/p65; (2) inhibit the expression of inflammatory genes that function downstream of RelA/p65; (3) inhibit chronic inflammation; (4) ameliorate lung pathology; (5) promote clearance of tuberculosis; and (6) enhance efficacy of anti-TB drugs (Figure 1).
Together, pharmacological formulations encompassing “Probiotic Lactobacillus gasseri SBT2055 or its analogues, either alone or in combination with other anti-TB drugs,“ may be used to treat drug-resistant tuberculosis.
Details of the research findings:
Idea roposed/Formulated by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How Probiotic Lactobacillus gasseri SBT2055 deacetylates RelA/p65 to combat drug-resistant tuberculosis
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Citation: Boominathan, L., Probiotic-based therapy for tuberculosis: Probiotic Lactobacillus gasseri SBT2055 deacetylates RelA/p65, inhibits inflammatory gene expression downstream of RelA/p65, inhibits TB pathogenesis, increases the efficacy of anti-TB drug, and promotes M. tuberculosis clearance via upregulation of its target gene, 11/October/2018, 12.01 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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