{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:12:59Z","timestamp":1793229179294,"version":"4.5.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mtb subverts host immune surveillance by damaging phagolysosomal membranes, exploiting them as replication niches. In response, host cells initiate a coordinated LDR, integrating membrane repair, selective autophagy, and de novo biogenesis. This review delineates a systems-level model of lysosomal quality control governed by three critical regulatory axes: LGALS3\/8\/9, TRIM E3 ubiquitin ligases, and the AMPK-TFEB signaling pathway. LGALSs detect exposed glycans on ruptured membranes, triggering ESCRT-mediated repair and recruiting ARs. TRIM proteins mediate context-specific ubiquitination, enhancing cargo selection and facilitating transcriptional reprogramming via TFEB. Simultaneously, AMPK-TFEB signaling links metabolic stress to lysosomal regeneration, reinforcing immune defense and cellular adaptation. We highlight emerging mechanisms, including ATG8ylation, CASM, Ca2\u00a0+\u00a0leakage, and SG formation, that refine this multilayered response. Mtb virulence factors selectively disrupt these pathways, revealing their relevance to pathogen persistence. Beyond infection, this triadic network maintains lysosomal integrity in neurodegeneration, inflammation, and lysosomal storage disorders. Understanding its modular design reveals novel therapeutic targets and HDTs for combatting drug-resistant TB. This review integrates recent advances into a coherent framework that redefines lysosomal function as a dynamic, immune-regulatory hub essential for cellular resilience under infectious and metabolic stress.<\/jats:p>","DOI":"10.1093\/femsre\/fuaf040","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T11:23:25Z","timestamp":1756725805000},"source":"Crossref","is-referenced-by-count":4,"title":["Exploring the multilayered response of TB bacterium\n                    <i>Mycobacterial tuberculosis<\/i>\n                    to lysosomal injury"],"prefix":"10.1093","author":[{"given":"Mohd","family":"Shariq","sequence":"first","affiliation":[{"name":"GITAM School of Science, GITAM University , Hyderabad, Telangana 502329 ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javaid Ahmad","family":"Sheikh","sequence":"additional","affiliation":[{"name":"School of Chemical and Life Sciences, Jamia Hamdard Department of Biotechnology, , New Delhi 110062"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asrar Ahmad","family":"Malik","sequence":"additional","affiliation":[{"name":"School of Basic Sciences and Research, Sharda University Department of Life Sciences, , Knowledge Park III, Greater Noida, Uttar Pradesh 201306"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anwar","family":"Alam","sequence":"additional","affiliation":[{"name":"School of Basic Sciences and Research, Sharda University Department of Life Sciences, , Knowledge Park III, Greater Noida, Uttar Pradesh 201306"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter N","family":"Monk","sequence":"additional","affiliation":[{"name":"Immunity and Cardiovascular Disease, Medical School, University of Sheffield Department of Infection, , Western Bank, Sheffield S10 2TN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed E","family":"Hasnain","sequence":"additional","affiliation":[{"name":"School of Basic Sciences and Research, Sharda University Department of Life Sciences, , Knowledge Park III, Greater Noida, Uttar Pradesh 201306"},{"name":"Indian Institute of Technology, Delhi (IIT-D) Department of Biochemical Engineering and Biotechnology, , Hauz Khas, New Delhi 110 016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasreen Z","family":"Ehtesham","sequence":"additional","affiliation":[{"name":"School of Basic Sciences and Research, Sharda University Department of Life Sciences, , Knowledge Park III, Greater Noida, Uttar Pradesh 201306"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,2]]},"container-title":["FEMS Microbiology Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/femsre\/advance-article-pdf\/doi\/10.1093\/femsre\/fuaf040\/64191321\/fuaf040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/femsre\/advance-article-pdf\/doi\/10.1093\/femsre\/fuaf040\/64191321\/fuaf040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T13:16:56Z","timestamp":1756819016000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/femsre\/advance-article\/doi\/10.1093\/femsre\/fuaf040\/8245870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/femsre\/fuaf040","relation":{},"ISSN":["0168-6445","1574-6976"],"issn-type":[{"value":"0168-6445","type":"print"},{"value":"1574-6976","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"article-number":"fuaf040"}}