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Several cellular functions of TA systems have been proposed however, their exact role in cellular physiology remains unresolved.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This study aims to find out the impact of the <jats:italic>mazEF<\/jats:italic> toxin\u2013antitoxin module on biofilm formation, pathogenesis, and antibiotic resistance in an isolated clinical ST239 MRSA strain, by constructing <jats:italic>mazE<\/jats:italic> and <jats:italic>mazF<\/jats:italic> mutants using CRISPR\u2013cas9 base-editing plasmid (pnCasSA-BEC). Transcriptome analysis (RNA-seq) was performed for the <jats:italic>mazE<\/jats:italic> antitoxin mutant in order to identify the differentially regulated genes. The biofilm formation was also assessed for the mutant strains. Antibiogram profiling was carried out for both the generated mutants followed by murine experiment to determine the pathogenicity of the constructed strains.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>For the first time our work showed, that MazF promotes <jats:italic>cidA<\/jats:italic> mediated cell death and lysis for biofilm formation without playing any significant role in host virulence as suggested by the murine experiment. Interestingly, the susceptibility to oxacillin, daptomycin and vancomycin was reduced significantly by the activated MazF toxin in the <jats:italic>mazE<\/jats:italic> mutant strain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study reveals that activated MazF toxin leads to resistance to antibiotics like oxacillin, daptomycin and vancomycin. Therefore, in the future, any potential antibacterial drug can be designed to target MazF toxin against the problematic multi-drug resistant bug.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12929-022-00810-5","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T02:06:47Z","timestamp":1651889207000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Unravelling the physiological roles of mazEF toxin\u2013antitoxin system on clinical MRSA strain by CRISPR RNA-guided cytidine deaminase"],"prefix":"10.1186","volume":"29","author":[{"given":"Sonia","family":"Jain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arghya","family":"Bhowmick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bohyun","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeok","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhrajyoti","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,7]]},"reference":[{"key":"810_CR1","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","volume":"28","author":"SYC Tong","year":"2015","unstructured":"Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. 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The followed animal study protocol was approved by the Committee on the Ethics of Animal Experiments of the Indiana University School of Medicine-Northwest (Protocol Number: NW-48). Every possible effort was made to lessen the suffering of the animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A patent has been accepted for clinical <i>S. aureus mazE<\/i> mutant with application no. 2021\/06280 on 8th October 2021.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"28"}}