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MAIT cells are innate-like T cells enriched in mucosal tissues with potent antimicrobial activity. Restoring their function may offer a host-directed strategy against drug-resistant pathogens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated how cognate antigen in combination with cytokines modulates MAIT cell cytotoxicity and enhances carbapenem activity. MAIT cell cytolytic protein expression, cytotoxicity, and effector function were measured after stimulation. Secretomes from activated MAIT cells were tested against engineered Escherichia coli expressing clinically relevant carbapenemases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Under optimal conditions, MAIT cells upregulated antimicrobial cytolytic proteins and efficiently killed antigen-pulsed target cells. Interleukin (IL)-15 or IL-2 plus IL-7 most effectively promoted polyfunctional cytotoxic responses. Secretomes from cytokine-stimulated MAIT cells restored imipenem activity against Escherichia coli expressing blaNDM-1, blaKPC-2, and blaOXA-48, reducing metabolic activity, viability, and growth. Notably, IL-2 plus IL-7 enabled expansion and functional restoration of MAIT cells from HAI patients with diminished baseline numbers and responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Tailored antigen and cytokine stimulation reinvigorates MAIT cell effector function and augments carbapenem efficacy, supporting MAIT cell-based host-directed adjunct strategies against AMR in vulnerable patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag151","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T12:47:54Z","timestamp":1774010874000},"page":"e1203-e1214","source":"Crossref","is-referenced-by-count":1,"title":["Restoration of Mucosa-Associated Invariant T-Cell Function in Healthcare-Associated Bacterial Infections Supports Recovery of Carbapenem Efficacy Against Resistant Bacteria Ex Vivo"],"prefix":"10.1093","volume":"233","author":[{"given":"Yiting","family":"Xue","sequence":"first","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-7090","authenticated-orcid":false,"given":"Asad Mustafa","family":"Karim","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2694-4192","authenticated-orcid":false,"given":"Wan Rong","family":"Sia","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School , , Singapore","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1478-9559","authenticated-orcid":false,"given":"Fei","family":"Han","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University , Shenzhen ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4289-3513","authenticated-orcid":false,"given":"Kai Lin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Singapore General Hospital , , Singapore","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-300X","authenticated-orcid":false,"given":"Nathalie Grace","family":"Chua","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Singapore General Hospital , , Singapore","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Hadadi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne and Lausanne University Hospital , Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Tsinghua University , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-4539","authenticated-orcid":false,"given":"Jeffrey Y W","family":"Mak","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery, Institute for Molecular Bioscience, The University of Queensland , Brisbane, QLD ,","place":["Australia"]},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland , Brisbane, QLD ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Fairlie","sequence":"additional","affiliation":[{"name":"Centre for Chemistry and Drug Discovery, Institute for Molecular Bioscience, The University of Queensland , Brisbane, QLD ,","place":["Australia"]},{"name":"Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland , Brisbane, QLD ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2752-0535","authenticated-orcid":false,"given":"Lin-Fa","family":"Wang","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School , , Singapore","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan K","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-4411","authenticated-orcid":false,"given":"Andrea Lay-Hoon","family":"Kwa","sequence":"additional","affiliation":[{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School , , Singapore","place":["Singapore"]},{"name":"Department of Pharmacy, Singapore General Hospital , , Singapore","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0505-4967","authenticated-orcid":false,"given":"Edwin","family":"Leeansyah","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University , Shenzhen ,","place":["China"]},{"name":"Programme in Emerging Infectious Diseases, Duke-NUS Medical School , , Singapore","place":["Singapore"]},{"name":"Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"2026051419565651000_jiag151-B1","doi-asserted-by":"crossref","first-page":"e20561","DOI":"10.1016\/j.heliyon.2023.e20561","article-title":"The burden of hospital acquired infections and antimicrobial resistance","volume":"9","author":"Abban","year":"2023","journal-title":"Heliyon"},{"key":"2026051419565651000_jiag151-B2","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1056\/NEJMra0904124","article-title":"Hospital-acquired infections due to gram-negative bacteria","volume":"362","author":"Peleg","year":"2010","journal-title":"N Engl J 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