{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:42:35Z","timestamp":1792291355994,"version":"4.4.0"},"reference-count":56,"publisher":"National Academy of Sciences","issue":"27","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IOS1754995"],"award-info":[{"award-number":["IOS1754995"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["IOS1755286"],"award-info":[{"award-number":["IOS1755286"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,7,4]]},"abstract":"<jats:p>\n                    Modern infectious disease outbreaks often involve changes in host tropism, the preferential adaptation of pathogens to specific hosts. The Lyme disease-causing bacterium\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    (\n                    <jats:italic>Bb<\/jats:italic>\n                    ) is an ideal model to investigate the molecular mechanisms of host tropism, because different variants of these tick-transmitted bacteria are distinctly maintained in rodents or bird reservoir hosts. To survive in hosts and escape complement-mediated immune clearance,\n                    <jats:italic>Bb<\/jats:italic>\n                    produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants differ in human FH-binding ability. Together with the FH polymorphisms between vertebrate hosts, these findings suggest that minor sequence variation in this bacterial outer surface protein may confer dramatic differences in host-specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ\u2013human FH complex, and identifying minor variation localized in the FH-binding interface yielding bird and rodent FH-specific binding activity that impacts infectivity. Swapping the divergent region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. We further linked these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ phylogenetic lineages, elucidating evolutionary mechanisms driving host tropism emergence. Our multidisciplinary work provides a novel molecular basis for how a single, short protein motif could greatly modulate pathogen host tropism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2301549120","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T15:09:49Z","timestamp":1687792189000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":25,"title":["Structural evolution of an immune evasion determinant shapes pathogen host tropism"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1417-5699","authenticated-orcid":false,"given":"Ashley L.","family":"Marcinkiewicz","sequence":"first","affiliation":[{"name":"New York State Department of Health, Division of Infectious Diseases, Wadsworth Center, Albany, NY 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Albany, NY 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inara","family":"Akopjana","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andris","family":"Kazaks","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janis","family":"Bogans","sequence":"additional","affiliation":[{"name":"Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6589-4728","authenticated-orcid":false,"given":"Alexander T.","family":"Ciota","sequence":"additional","affiliation":[{"name":"New York State Department of Health, Division of Infectious Diseases, Wadsworth Center, Albany, NY 12208"},{"name":"Department of Biomedical Sciences, State University of New York Albany, Albany, NY 12222"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kraiczy","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe University Frankfurt, Frankfurt 60596, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3309-8465","authenticated-orcid":false,"given":"Sergios-Orestis","family":"Kolokotronis","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Brooklyn, NY 11203-2098"},{"name":"Institute for Genomics in Health, Brooklyn, NY 11203-2098"},{"name":"Division of Infectious Diseases, Department of Medicine, College of Medicine, Brooklyn, NY 11203-2098"},{"name":"Department of Cell Biology, College of Medicine, State University of New York Downstate Health Sciences University, Brooklyn, NY 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