{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:52Z","timestamp":1785437992209,"version":"3.56.0"},"posted":{"date-parts":[[2025,12,4]]},"group-title":"Biochemistry","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["I-1686"],"award-info":[{"award-number":["I-1686"]}],"id":[{"id":"https:\/\/ror.org\/00np6vq88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21AI183574"],"award-info":[{"award-number":["R21AI183574"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/039djdh30","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Chilton Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Pertussis (whooping cough) is caused by the bacterium\n                  <jats:italic>Bordetella pertussis<\/jats:italic>\n                  . Among the virulence factors produced by\n                  <jats:italic>B. pertussis,<\/jats:italic>\n                  pertussis toxin (PT) is responsible for key disease symptoms, including impacts on the immune system. PT is an AB\n                  <jats:sub>5<\/jats:sub>\n                  toxin, consisting of a single catalytic A subunit and five B subunits. The B pentamer recognizes cell surface glycans and facilitates intracellular delivery of the catalytic A subunit. PT also impacts host cell signaling via mechanisms that do not depend on the catalytic activity of the A subunit. In particular, PT promotes signaling through the T-cell receptor (TCR), leading to activation of extracellular signal-regulated kinase (ERK) cascades. PT prefers to bind sialylated and N-linked glycans, but other aspects of PT\u2019s glycan binding specificity remain underexplored. Here we report that the absence of fucose on mammalian cell surfaces leads to increased binding by PT. Using pharmacological inhibitors in a human bronchial epithelial cell line, we observe that sialylation and N-linked glycosylation promote PT binding while fucosylation interferes with PT binding. Similarly, CHO and Colo205 cells deficient in fucosylation exhibited enhanced PT binding as compared to the corresponding wild-type cell lines. Genetic knockout of FUT3\/FUT5\/FUT6 or of FUT8 led to increased PT binding, suggesting that specific fucosylated epitopes mediate protection from PT. The functional impact of altered PT binding was examined in Jurkat T cells, where removal of cell surface non-core fucose led to increased PT-dependent ERK phosphorylation. In sum, our study identifies a role for fucosylation in protecting mammalian cells from PT.\n                <\/jats:p>","DOI":"10.64898\/2025.12.03.692184","type":"posted-content","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T12:42:01Z","timestamp":1765197721000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypofucosylation promotes pertussis toxin binding to cell surface glycococonjugates and pertussis toxin-induced intracellular ERK signaling"],"prefix":"10.64898","author":[{"given":"Rohit Sai Reddy","family":"Konada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Nischan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5373-3329","authenticated-orcid":false,"given":"Jennifer J.","family":"Kohler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025120808201287000_2025.12.03.692184v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa469"},{"key":"2025120808201287000_2025.12.03.692184v1.2","doi-asserted-by":"publisher","DOI":"10.1086\/589753"},{"key":"2025120808201287000_2025.12.03.692184v1.3","doi-asserted-by":"publisher","DOI":"10.1080\/00365540510026436"},{"key":"2025120808201287000_2025.12.03.692184v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.2.326-382.2005"},{"key":"2025120808201287000_2025.12.03.692184v1.5","first-page":"373","article-title":", the causative agent of whooping cough, evolved from a distinct, human-associated lineage of","volume":"1","year":"2005","journal-title":"Plos Pathogens"},{"key":"2025120808201287000_2025.12.03.692184v1.6","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00083-15"},{"key":"2025120808201287000_2025.12.03.692184v1.7","doi-asserted-by":"crossref","unstructured":"Esposito, S. , Stefanelli, P. , Fry, N. K. , Fedele, G. , He, Q. S. , Paterson, P. , Tan, T. N. , Knuf, M. , Rodrigo, C. , Olivier, C. W. , Flanagan, K. L. , Hung, I. , Lutsar, I. , Edwards, K. , O\u2019Ryan, M. , Principi, N. , Immunologic, W. A. I. D. , and In, E. S. C. M . (2019) Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines. Frontiers in Immunology 10","DOI":"10.3389\/fimmu.2019.01344"},{"key":"2025120808201287000_2025.12.03.692184v1.8","unstructured":"United States Centers for Disease Control and Prevention. Manual for the Surveillance of Vaccine-Preventable Diseases. ( Roush, S. W. , Baldy, L. 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