Intestinal microbiota disruption limits the isoniazid mediated clearance ofMycobacterium tuberculosisin mice
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
Intestinal microbiota disruption limits the isoniazid mediated clearance ofMycobacterium tuberculosisin mice
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| Creator |
Negi, Shikha
Pahari, Susanta Bashir, Hilal Agrewala, J N |
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| Subject |
QR Microbiology
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| Description |
Tuberculosis (TB) continues to remain a global threat due to the emergence of drug-resistantMycobacterium tuberculosis(Mtb) strains and toxicity associated with TB drugs. Intestinal microbiota has been reported to affect the host response to immunotherapy and drugs. However, how it affects the potency of first-line TB drug isoniazid (INH) is largely unknown. Here, we examined the impact of gut microbial dysbiosis on INH efficiency to killMtb. In this study, we employed in vivo mouse model, pretreated with broad-spectrum antibiotics (Abx) cocktail to disrupt their intestinal microbial population prior toMtbinfection and subsequent INH therapy. We demonstrated that microbiota disruption results in the impairment of INH-mediatedMtbclearance, and aggravated TB-associated tissue pathology. Further, it suppressed the innate immunity and reduced CD4 T-cell response againstMtb. Interestingly, a distinct shift of gut microbial profile was noted with abundance ofEnterococcusand reduction ofLactobacillusandBifidobacteriumpopulation. Our results show that the intestinal microbiota is crucial determinant in efficacy of INH to killMtband impacts the host immune response against infection. This work provides an intriguing insight into the potential links between host gut microbiota and potency of INH.
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| Publisher |
Wiley
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| Date |
2020-07-16
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| Type |
Article
PeerReviewed |
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| Relation |
https://onlinelibrary.wiley.com/doi/abs/10.1002/eji.202048556
http://crdd.osdd.net/open/2596/ |
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| Identifier |
Negi, Shikha and Pahari, Susanta and Bashir, Hilal and Agrewala, J N (2020) Intestinal microbiota disruption limits the isoniazid mediated clearance ofMycobacterium tuberculosisin mice. European journal of immunology. ISSN 0014-2980 (In Press)
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