{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T06:32:31Z","timestamp":1782801151579,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012032","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T00:00:00Z","timestamp":1709683200000}}],"reference-count":105,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T00:00:00Z","timestamp":1708646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI093858, AI074789, AI138129, and AI119873"],"award-info":[{"award-number":["AI093858, AI074789, AI138129, and AI119873"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"crossref","award":["5P41RR011823"],"award-info":[{"award-number":["5P41RR011823"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["8P41 GM103533"],"award-info":[{"award-number":["8P41 GM103533"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["Z01 AI001337-01"],"award-info":[{"award-number":["Z01 AI001337-01"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Lyme disease (LD) caused by <jats:italic>Borrelia burgdorferi<\/jats:italic> is among the most important human vector borne diseases for which there is no effective prevention method. Identification of tick saliva transmission factors of the LD agent is needed before the highly advocated tick antigen-based vaccine could be developed. We previously reported the highly conserved <jats:italic>Ixodes scapularis<\/jats:italic> (<jats:italic>Ixs<\/jats:italic>) tick saliva serpin (S) 17 (<jats:italic>Ixs<\/jats:italic>S17) was highly secreted by <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> infected nymphs. Here, we show that <jats:italic>Ixs<\/jats:italic>S17 promote tick feeding and enhances <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> colonization of the host. We show that <jats:italic>Ixs<\/jats:italic>S17 is not part of a redundant system, and its functional domain reactive center loop (RCL) is 100% conserved in all tick species. Yeast expressed recombinant (r) <jats:italic>Ixs<\/jats:italic>S17 inhibits effector proteases of inflammation, blood clotting, and complement innate immune systems. Interestingly, differential precipitation analysis revealed novel functional insights that <jats:italic>Ixs<\/jats:italic>S17 interacts with both effector proteases and regulatory protease inhibitors. For instance, r<jats:italic>Ixs<\/jats:italic>S17 interacted with blood clotting proteases, fXII, fX, fXII, plasmin, and plasma kallikrein alongside blood clotting regulatory serpins (antithrombin III and heparin cofactor II). Similarly, r<jats:italic>Ixs<\/jats:italic>S17 interacted with both complement system serine proteases, C1s, C2, and factor I and the regulatory serpin, plasma protease C1 inhibitor. Consistently, we validated that r<jats:italic>Ixs<\/jats:italic>S17 dose dependently blocked deposition of the complement membrane attack complex via the lectin complement pathway and protected complement sensitive <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> from complement-mediated killing. Likewise, co-inoculating C3H\/HeN mice with r<jats:italic>Ixs<\/jats:italic>S17 and <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> significantly enhanced colonization of mouse heart and skin organs in a reverse dose dependent manner. Taken together, our data suggests an important role for <jats:italic>Ixs<\/jats:italic>S17 in tick feeding and <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> colonization of the host.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012032","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T19:14:27Z","timestamp":1708715667000},"page":"e1012032","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["A tick saliva serpin, IxsS17 inhibits host innate immune system proteases and enhances host colonization by Lyme disease agent"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3678-9414","authenticated-orcid":true,"given":"Thu-Thuy","family":"Nguyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Heung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Bencosme-Cuevas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquie","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex Samuel Kiarie","family":"Gaithuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moiz Ashraf","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Kwon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Tirloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeljko","family":"Radulovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Moresco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Yates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5029-1198","authenticated-orcid":true,"given":"Albert","family":"Mulenga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"issue":"9127","key":"ppat.1012032.ref001","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0140-6736(98)01146-5","article-title":"Lyme borreliosis.","volume":"352","author":"RB Nadelman","year":"1998","journal-title":"Lancet"},{"key":"ppat.1012032.ref002","doi-asserted-by":"crossref","DOI":"10.1017\/S0031182003004694","article-title":"Lyme borreliosis in Europe and North America","volume":"129","author":"J Piesman","year":"2004","journal-title":"Parasitology"},{"issue":"2","key":"ppat.1012032.ref003","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.idc.2015.02.010","article-title":"Epidemiology of Lyme disease.","volume":"29","author":"PS Mead","year":"2015","journal-title":"Infect Dis Clin North Am"},{"issue":"5","key":"ppat.1012032.ref004","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S1473-3099(15)00464-8","article-title":"Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study","volume":"16","author":"BS Pritt","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"ppat.1012032.ref005","first-page":"1164","article-title":"Prevention of Lyme disease.","volume":"49","author":"P Couch","year":"1992","journal-title":"Am J Hosp Pharm"},{"issue":"3","key":"ppat.1012032.ref006","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1603\/0022-2585-39.3.509","article-title":"Protection against lyme disease spirochete transmission provided by prompt removal of nymphal Ixodes scapularis (Acari: Ixodidae).","volume":"39","author":"J Piesman","year":"2002","journal-title":"J Med Entomol"},{"issue":"4","key":"ppat.1012032.ref007","doi-asserted-by":"crossref","first-page":"101944","DOI":"10.1016\/j.ttbdis.2022.101944","article-title":"Personal protection measures to prevent tick bites in the United States: Knowledge gaps, challenges, and opportunities.","volume":"13","author":"L. 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