{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:01:30Z","timestamp":1792807290677,"version":"4.5.0"},"reference-count":153,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council of Hong Kong","award":["T13-605\/18W"],"award-info":[{"award-number":["T13-605\/18W"]}]},{"name":"Areas of Excellence Scheme of the University Grants Committee","award":["AoE\/M-604\/16"],"award-info":[{"award-number":["AoE\/M-604\/16"]}],"id":[{"id":"https:\/\/ror.org\/00djwmt25","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Innovation and Technology Commission of the HKSAR Government","award":["INNOHK18SC01"],"award-info":[{"award-number":["INNOHK18SC01"]}],"id":[{"id":"https:\/\/ror.org\/04vf9tr09","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Innovation and Technology Commission of the HKSAR Government","award":["ITCPD\/17-9"],"award-info":[{"award-number":["ITCPD\/17-9"]}],"id":[{"id":"https:\/\/ror.org\/04vf9tr09","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007937","name":"Peking University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007937","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Pertussis toxin (PTx) is a major virulence factor of Bordetella pertussis and an AB5-type exotoxin that disrupts host signaling. Its enzymatic A subunit ADP-ribosylates the \u03b1-subunit of inhibitory G proteins (G\u03b1i), preventing them from mediating receptor-induced inhibition of adenylyl cyclase (AC). This leads to unrestrained cAMP accumulation in host cells, a canonical mechanism underlying many pertussis disease manifestations. PTx works in concert with the bacterium\u2019s adenylate cyclase toxin (ACT) to subvert immune defenses and establish infection. Interestingly, PTx exerts both cAMP-dependent and cAMP-independent effects. In addition to the well-known cAMP-mediated pathway, PTx\u2019s B oligomer can engage host cell surface receptors to trigger signaling cascades independent of the A subunit\u2019s catalytic activity. Such B oligomer-mediated pathways modulate cellular responses in the absence of ADP-ribosylation. This review provides a comprehensive analysis of PTx\u2019s dual functionality, distinguishing its Gi protein-dependent elevation of cAMP from the noncanonical activities of the B oligomer. It also highlights how disruption of constitutive Gi signaling and the interplay between PTx and ACT shape host\u2013pathogen interaction in pertussis pathogenesis.<\/jats:p>","DOI":"10.3390\/toxins18030148","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T14:14:05Z","timestamp":1773843245000},"page":"148","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms of Pertussis Toxin Action: ADP-Ribosylation and Its Role in Pertussis Pathogenesis"],"prefix":"10.3390","volume":"18","author":[{"given":"Qing","family":"Tang","sequence":"first","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China"},{"name":"Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-5573","authenticated-orcid":false,"given":"Ho Yung","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-2028","authenticated-orcid":false,"given":"Yanxi","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China"},{"name":"Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen 518132, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0123-7697","authenticated-orcid":false,"given":"Yung H.","family":"Wong","sequence":"additional","affiliation":[{"name":"Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Hong Kong, China"},{"name":"State Key Laboratory of Nervous System Disorders and the Daniel and Mayce Yu Molecular Neuroscience Center, Hong Kong University of Science and Technology, Hong Kong, China"},{"name":"InnoHK Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1128\/CMR.18.2.326-382.2005","article-title":"Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies","volume":"18","author":"Mattoo","year":"2005","journal-title":"Clin. 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