{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:38Z","timestamp":1785416498968,"version":"3.56.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR39006\/BRB\/10\/1883\/2020, BT\/PR24443\/MED\/29\/1220\/2017"],"award-info":[{"award-number":["BT\/PR39006\/BRB\/10\/1883\/2020, BT\/PR24443\/MED\/29\/1220\/2017"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Tuberculosis is caused by the bacterium\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis (Mtb<\/jats:italic>\n                      ). Emergence of drug resistance in\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      requires continuous enrichment of anti-tubercular medication. Inclusion of host-directed therapies holds considerable promise in this context. Sorafenib (SRB) is a multi-kinase inhibitor targeting VEGF receptor kinase, Raf, MEK, and extracellular signal-regulated kinase (ERK) signaling cascade to treat several types of cancer, including hepatocellular carcinoma. We have previously established that SRB allosterically inhibits ornithine acetyltransferase (MtArgJ), an essential enzyme in the arginine biosynthesis pathway of\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      , thereby limiting bacterial growth in culture at a minimum inhibitory concentration of 10 \u00b5g\/mL. The current work focuses on how SRB at the dose of 30 mg\/kg body wt inhibits the pathogenicity and survival of bacteria in a preclinical mouse model of tuberculosis by inducing pro-apoptotic and immunomodulatory mechanisms in the host. We observed that SRB treatment promotes apoptosis in\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      -infected and -uninfected THP-1 cells, human monocyte-derived macrophages. Concomitantly, SRB treatment reduces infection-associated necrosis in the\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      -infected THP-1 cells. We further noted the upregulated expression of pro-apoptotic proteins during SRB treatment in preclinical mouse models. In addition, we investigated the expression of pro- and anti-inflammatory cytokines and immunomodulation in lung tissues treated with SRB. Interestingly, SRB treatment increased the number of arginase 1-positive macrophages, which are reckoned to enhance tissue healing. In conclusion, our research discloses that SRB is helpful in both lowering the tubercular burden and accelerating recovery of damaged tissue by harnessing the host immune response.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Host-directed therapies hold considerable promise for treating drug-resistant\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        (\n                        <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                        ). In this context, the induction of apoptotic and immunomodulatory responses in the host by sorafenib (SRB) is demonstrated here to compromise the survival and pathogenic potential of\n                        <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                        in a preclinical mouse model of TB and in\n                        <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                        -infected and -uninfected THP-1 cells. Concurrently, the infection-associated necrosis in the\n                        <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                        -infected THP-1 cells is also reduced. Furthermore, arginase 1-positive macrophages, which are known to enhance tissue healing, are increased in SRB-treated groups. Thus, SRB treatment not only lowers the tubercular load but also aids in healing damaged tissues by leveraging the host immunity.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01657-25","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T14:00:21Z","timestamp":1769436021000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The antimycobacterial and healing effect of sorafenib through pro-apoptotic and immunomodulatory activities"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0463-8461","authenticated-orcid":false,"given":"Raju S.","family":"Rajmani","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05j873a45","id-type":"ROR","asserted-by":"publisher"}],"name":"Molecular Biophysics Unit, Indian Institute of Science","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Rani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05j873a45","id-type":"ROR","asserted-by":"publisher"}],"name":"Molecular Biophysics Unit, Indian Institute of Science","place":["Bangalore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-9095","authenticated-orcid":true,"given":"Avadhesha","family":"Surolia","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05j873a45","id-type":"ROR","asserted-by":"publisher"}],"name":"Molecular Biophysics Unit, Indian Institute of Science","place":["Bangalore, India"]},{"name":"Dr. Reddy's Institute of Life Sciences","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2024. Global tuberculosis report 2024. Available from: https:\/\/www.who.int\/teams\/global-tuberculosis-programme\/tb-reports\/global-tuberculosis-report-2024. Retrieved 25 Nov 2024."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.163.5.2007122"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.14-3-279"},{"key":"e_1_3_3_5_2","first-page":"429","article-title":"Differential proteomics approach to identify putative protective antigens of Mycobacterium tuberculosis presented during early stages of macrophage infection and their evaluation as DNA vaccines","volume":"53","author":"Sharma S","year":"2015","unstructured":"Sharma S, Rajmani RS, Kumar A, Bhaskar A, Singh A, Manivel V, Tyagi AK, Rao KVS. 2015. Differential proteomics approach to identify putative protective antigens of Mycobacterium tuberculosis presented during early stages of macrophage infection and their evaluation as DNA vaccines. 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