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As a response, <jats:italic>M. tuberculosis<\/jats:italic> codes for short-chain dehydrogenases\/reductases (SDRs). These SDRs are nicotinamide adenine dinucleotide-reliant oxidoreductases involved in cell homeostasis. The precise function of oxidoreductases in bacteria especially <jats:italic>M. tuberculosis<\/jats:italic> were not fully explored. This study aimed to know the detail functional role of one of the oxidoreductase Rv0148 in <jats:italic>M. tuberculosis.<\/jats:italic><\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>In silico analysis revealed that Rv0148 interacts with Htdy (Rv3389) and the protein interactions were confirmed using far western blot. Gene knockout mutant of Rv0148 in <jats:italic>M. tuberculosis<\/jats:italic> was constructed by specialized transduction. Macrophage cell line infection with this knockout mutant showed increased expression of pro-inflammatory cytokines. This knockout mutant is sensitive to oxidative, nitrogen, redox and electron transport inhibitor stress agents. Drug susceptibility testing of the deletion mutant showed resistance to first-line drugs such as streptomycin and ethambutol and second-line aminoglycosides such as amikacin and kanamycin. Based on interactorme analysis for Rv0148 using STRING database, we identified 220 most probable interacting partners for\u00a0Htdy protein. In the Rv0148 knockout mutants, high expression of <jats:italic>htdy<\/jats:italic> was observed and we hypothesize that this would have perturbed the interactome thus resulting in drug resistance. Finally, we propose that Rv0148 and Htdy are functionally interconnected and involved in drug resistance and cell homeostasis of <jats:italic>M. tuberculosis.<\/jats:italic><\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our study suggests that Rv0148 plays a significant role in various functional aspects such as intermediatory metabolism, stress, homeostasis and also in drug resistance.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12866-020-01763-1","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T15:03:29Z","timestamp":1586963009000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Protein\u2013protein interaction of Rv0148 with Htdy and its predicted role towards drug resistance in Mycobacterium tuberculosis"],"prefix":"10.1186","volume":"20","author":[{"given":"Gunapati","family":"Bhargavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramanyam","family":"Balaji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth Prasad","family":"Tripathy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kannan","family":"Palaniyandi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"1763_CR1","unstructured":"Kyu HH, Maddison ER, Henry NJ, Mumford JE, Mumford JE, Shields C. 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