{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:05:08Z","timestamp":1770275108736,"version":"3.49.0"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI 141877"],"award-info":[{"award-number":["AI 141877"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                    <\/jats:styled-content>\n                    is a leading cause of bacterial community\u2010acquired pneumonia, responsible for severe respiratory and extrapulmonary diseases in children and adults. The Community Acquired Respiratory Distress Syndrome (CARDS) toxin is a key virulence factor that exerts ADP\u2010ribosylating and vacuolating activities on host cells, recapitulating the inflammatory and histopathological damage seen in infected airways. Although the host proteins annexin\u2010A2 (AnxA2) and surfactant protein\u2010A were previously identified as toxin receptors, their absence did not abrogate CARDS toxin activity. Intriguingly, our subsequent work identified an interaction between CARDS toxin and the ubiquitous membrane phospholipids sphingomyelin (SM) and phosphatidylcholine (PC). This study investigated whether CARDS toxin uses these lipids as functional cell surface receptors. Using enzyme\u2010linked immunosorbent assays, we demonstrated that the carboxy region of CARDS toxin binds to SM and PC in a dose\u2010dependent manner, exhibiting higher affinity for SM. Depletion of SM from airway epithelial cell surface significantly reduced CARDS toxin binding, internalization and retrograde transport, as shown by immunoblot, pull\u2010down, immunofluorescence, and live\u2010cell imaging. Furthermore, SM depletion markedly decreased toxin\u2010induced vacuolation and its stability, a phenotype rescued by adding exogenous SM. Notably, combining SM depletion with AnxA2 suppression nearly abolished toxin binding, entry, and subsequent vacuolation. These findings establish that CARDS toxin utilizes SM as a functional receptor to mediate its activity, highlighting a critical lipid\u2010dependent mechanism for host cell targeting.\n                  <\/jats:p>","DOI":"10.1111\/mmi.70044","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T12:00:31Z","timestamp":1767441631000},"page":"145-158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacterial Toxin Exploits Host Membrane Phospholipid as a Receptor for Binding, Entry, and Cytopathogenicity"],"prefix":"10.1111","volume":"125","author":[{"given":"Alejandra M.","family":"Kirkpatrick","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics The University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thirumalai R.","family":"Kannan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics The University of Texas Health Science Center at San Antonio  San Antonio Texas 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