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Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations<jats:italic>in vitro<\/jats:italic>, ACT has not been observed or quantified<jats:italic>in vivo<\/jats:italic>, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human and<jats:italic>in vitro<\/jats:italic>data, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to \u223c10<jats:sup>8<\/jats:sup>CFU\/ml<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pertussis<\/jats:named-content>and 1 to 5 ng\/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng\/ml ACT. When \u223c10<jats:sup>8<\/jats:sup>CFU\/ml of a laboratory strain of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. pertussis<\/jats:named-content>was cultured<jats:italic>in vitro<\/jats:italic>, ACT production was detected in 60 min and reached a plateau of \u223c60 ng\/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng\/ml, providing a reference point for future studies of ACT and pertussis pathogenesis.<\/jats:p>","DOI":"10.1128\/iai.00110-13","type":"journal-article","created":{"date-parts":[[2013,2,20]],"date-time":"2013-02-20T07:15:35Z","timestamp":1361344535000},"page":"1390-1398","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Quantification of the Adenylate Cyclase Toxin of Bordetella pertussis<i>In Vitro<\/i>and during Respiratory Infection"],"prefix":"10.1128","volume":"81","author":[{"given":"Joshua C.","family":"Eby","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary C.","family":"Gray","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Warfel","sequence":"additional","affiliation":[{"name":"Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Paddock","sequence":"additional","affiliation":[{"name":"Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara F.","family":"Jones","sequence":"additional","affiliation":[{"name":"Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shandra R.","family":"Day","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bowden","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia Medical Center, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda D.","family":"Poulter","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia Medical Center, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina M.","family":"Donato","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod J.","family":"Merkel","sequence":"additional","affiliation":[{"name":"Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik L.","family":"Hewlett","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"744","article-title":"Pertussis of adults and infants","volume":"2","author":"von Konig CHW","year":"2002","unstructured":"von KonigCHWHalperinSRiffelmannMGuisoN. 2002. 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