{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:13:04Z","timestamp":1790737984757,"version":"4.1.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI153160-A1, R21 AI177818, R01 AI129541, R01 AI43986, R01 AI094991"],"award-info":[{"award-number":["R01 AI153160-A1, R21 AI177818, R01 AI129541, R01 AI43986, R01 AI094991"]}],"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":[[2025,6,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Bordetella pertussis<\/jats:italic>\n                      , which causes the acute human disease whooping cough, evolved from\n                      <jats:italic toggle=\"yes\">Bordetella bronchiseptica<\/jats:italic>\n                      , which causes long-term, chronic infections in a broad range of mammals. Both\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">B. bronchiseptica<\/jats:italic>\n                      produce adenylate cyclase toxin (ACT), a bifunctional protein with adenylate cyclase-mediated cell intoxication and pore-forming activities. CyaC-mediated acylation of ACT is important for cell intoxication and required for pore-forming activity\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , but its role\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      was unknown. Our comparative analysis showed that although ACT secreted by\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      is fully acylated at residues K860 and K983, only a fraction of ACT secreted by\n                      <jats:italic toggle=\"yes\">B. bronchiseptica<\/jats:italic>\n                      is modified. We showed that\n                      <jats:italic toggle=\"yes\">B. bronchiseptica<\/jats:italic>\n                      produces more ACT than\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      and is more efficient at ACT-dependent intoxication of macrophages\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      than\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      , but for both organisms, acylation of ACT greatly enhances intoxication. Acylation also enhances ACT secretion. Using a natural-host model, we determined that non-acylated ACT is functional during the initial stage of\n                      <jats:italic toggle=\"yes\">B. bronchiseptica<\/jats:italic>\n                      infection, but not at later time points, and that acylation of K860, but not K983, is required for persistence in the lower respiratory tract. These data indicate a role for both acylated and non-acylated ACT during infection. Acylation of ACT was similarly not absolutely required for\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      persistence in the murine lower respiratory tract. Overall, our data revealed nuanced differences in production, acylation, and secretion of ACT between\n                      <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">B. bronchiseptica<\/jats:italic>\n                      that may correlate with their different virulence strategies.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Bordetella pertussis<\/jats:italic>\n                        causes the acute disease whooping cough and survives only in the human respiratory tract, while\n                        <jats:italic toggle=\"yes\">Bordetella bronchiseptica<\/jats:italic>\n                        causes long-term, chronic infections in a broad range of mammals and can also survive in extra-host environments. These bacteria produce a nearly identical set of virulence factors, including adenylate cyclase toxin (ACT), a protein that is modified by the addition of acyl chains. Acylation is required for ACT to cause hemolysis and for efficient intoxication of host cells\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        . We found that ACT acylation is also important, but not absolutely required, during infection. We also discovered differences in ACT production, acylation, and secretion between\n                        <jats:italic toggle=\"yes\">B. bronchiseptica<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">B. pertussis<\/jats:italic>\n                        that may contribute to the different virulence strategies of these species. This study highlights the advantage of conducting comparative analyses between closely related species to better understand the evolution of virulence.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01082-25","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T09:03:29Z","timestamp":1747645409000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Nuanced differences in adenylate cyclase toxin production, acylation, and secretion may contribute to the evolution of virulence in\n                    <i>Bordetella<\/i>\n                    species"],"prefix":"10.1128","volume":"16","author":[{"given":"Alexa R.","family":"Wolber","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina-Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana S.","family":"McKay","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina-Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katlyn B.","family":"Mote","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0130frc33","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, School of Medicine, University of North Carolina-Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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