{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:09:33Z","timestamp":1789877373405,"version":"4.0.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,23]],"date-time":"2018-01-23T00:00:00Z","timestamp":1516665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T00:00:00Z","timestamp":1520380800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Kleberg"},{"name":"NIH\/NCI","award":["P30 CA054174."],"award-info":[{"award-number":["P30 CA054174."]}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI070412"],"award-info":[{"award-number":["U19AI070412"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI118051"],"award-info":[{"award-number":["AI118051"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2018,3,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n            is an atypical bacterium that causes respiratory illnesses in humans, including pharyngitis, tracheobronchitis, and community-acquired pneumonia (CAP). It has also been directly linked to reactive airway disease, asthma, and extrapulmonary pathologies. During its colonization,\n            <jats:italic>M.\u00a0pneumoniae<\/jats:italic>\n            expresses a unique ADP-ribosylating and vacuolating cytotoxin designated\n            <jats:underline>c<\/jats:underline>\n            ommunity-\n            <jats:underline>a<\/jats:underline>\n            cquired\n            <jats:underline>r<\/jats:underline>\n            espiratory\n            <jats:underline>d<\/jats:underline>\n            istress\n            <jats:underline>s<\/jats:underline>\n            yndrome (CARDS) toxin. CARDS toxin persists and localizes in the airway in CAP patients, asthmatics, and trauma patients with ventilator-associated pneumonia. Although CARDS toxin binds to specific cellular receptors, is internalized, and induces hyperinflammation, histopathology, mucus hyperplasia, and other airway injury, the intracellular trafficking of CARDS toxin remains unclear. Here, we show that CARDS toxin translocates through early and late endosomes and the Golgi complex and concentrates at the perinuclear region to reach the endoplasmic reticulum (ER). Using ER-targeted SNAP-tag, we confirmed the association of CARDS toxin with the ER and determined that CARDS toxin follows the retrograde pathway. In addition, we identified a novel CARDS toxin amino acid fingerprint, KELED, that is required for toxin transport to the ER and subsequent toxin-mediated cytotoxicity.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n            , a leading cause of bacterial community-acquired pneumonia (CAP) among children and adults in the United States, synthesizes a 591-amino-acid ADP-ribosylating and vacuolating protein, designated\n            <jats:underline>c<\/jats:underline>\n            ommunity-\n            <jats:underline>a<\/jats:underline>\n            cquired\n            <jats:underline>r<\/jats:underline>\n            espiratory\n            <jats:underline>d<\/jats:underline>\n            istress\n            <jats:underline>s<\/jats:underline>\n            yndrome (CARDS) toxin. CARDS toxin alone is sufficient to induce and mimic major inflammatory and histopathological phenotypes associated with\n            <jats:italic>M. pneumoniae<\/jats:italic>\n            infection in rodents and primates. In order to elicit its ADP-ribosylating and vacuolating activities, CARDS toxin must bind to host cell receptors, be internalized via clathrin-mediated pathways, and subsequently be transported to specific intracellular organelles. Here, we demonstrate how CARDS toxin utilizes its unique KELED sequence to exploit the retrograde pathway machinery to reach the endoplasmic reticulum (ER) and fulfill its cytopathic potential. The knowledge generated from these studies may provide important clues to understand the mode of action of CARDS toxin and develop interventions that reduce or eliminate\n            <jats:italic>M. pneumoniae<\/jats:italic>\n            -associated airway and extrapulmonary pathologies.\n          <\/jats:p>","DOI":"10.1128\/mbio.01663-17","type":"journal-article","created":{"date-parts":[[2018,1,22]],"date-time":"2018-01-22T13:23:48Z","timestamp":1516627428000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["<i>Mycoplasma pneumoniae<\/i>\n            Community-Acquired Respiratory Distress Syndrome Toxin Uses a Novel KELED Sequence for Retrograde Transport and Subsequent Cytotoxicity"],"prefix":"10.1128","volume":"9","author":[{"given":"Kumaraguruparan","family":"Ramasamy","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sowmya","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan","family":"Manickam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya","family":"Pandranki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander B.","family":"Taylor","sequence":"additional","affiliation":[{"name":"X-Ray Crystallography Core Laboratory, Institutional Research Cores and Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. John","family":"Hart","sequence":"additional","affiliation":[{"name":"X-Ray Crystallography Core Laboratory, Institutional Research Cores and Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"},{"name":"Department of Veterans Affairs, South Texas Veterans Health Care System, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel B.","family":"Baseman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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