{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:58:54Z","timestamp":1785405534981,"version":"3.56.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/W016133\/1"],"award-info":[{"award-number":["BB\/W016133\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Leptospirosis is a globally significant severe infectious disease that affects a range of mammals. To understand its complex aetiopathogenesis,\n                      <jats:italic toggle=\"yes\">Leptospira<\/jats:italic>\n                      spp. are classified as pathogenic or saprophytic, with serum resistance a key differentiator of virulence. LIC13259 is a leptospiral surface lipoprotein that binds C8 of the host complement system; however, the molecular basis of this interaction has remained unclear. AlphaFold2 structural predictions, together with protein engineering, biochemical, and immunological validations, revealed that LIC13259 binds specifically to the C8\u03b3 subunit via thiol-disulfide exchange. Binding assays confirmed that LIC13259 from pathogenic, but not saprophytic,\n                      <jats:italic toggle=\"yes\">Leptospira<\/jats:italic>\n                      adheres to C8\u03b3, preventing C8\u03b1 binding, and enabling membrane attack complex evasion. Substitution of cysteine-133 with an alanine abolished both C8\u03b3 binding and complement inhibition. Removal (alanine substitution) of the target cysteine from C8\u03b3 prevented pathogenic LIC13259 binding, whereas removing LIC13259 cysteine-108, which forms a predicted intramolecular disulfide bond with cysteine-133, enhanced C8\u03b3 binding. These results identify an unprecedented cross-kingdom intermolecular disulfide bond mediating complement evasion and highlight the value of AlphaFold structural modeling, combined with targeted mutagenesis and biochemical validation, for discovering host-pathogen protein-protein interactions. The discovery of this novel immune evasion mechanism may allow recognition of this unique host-pathogen interaction in a range of diseases, while therapeutics and vaccines targeting such cross-kingdom disulfide-mediated mimicry may enable future infectious disease control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Leptospirosis is a globally important zoonotic disease of humans and animals, caused by the bacteria Leptospira. A central determinant of virulence is the ability for these bacteria to evade complement, a host defense system that assembles the membrane attack complex to eliminate pathogens. Here, we elucidate a novel immune evasion mechanism in which the leptospiral surface protein LIC13259 forms a disulfide bond with complement component C8\u03b3, preventing binding of C8\u03b1. This interaction disrupts the membrane attack complex assembly and promotes bacterial survival. To our knowledge, this represents the first example of a cross-kingdom disulfide bond mediating bacterial pathogenesis. These findings provide novel insights into leptospiral immune modulation and demonstrate the power of AlphaFold-based structural predictions to reveal unique host-pathogen interactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00878-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:00:40Z","timestamp":1781524840000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["AlphaFold reveals how pathogenic\n                    <i>Leptospira<\/i>\n                    use cross-kingdom thiol-disulfide exchange to evade the complement membrane attack complex"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4108-7603","authenticated-orcid":true,"given":"Abbie","family":"Hinds","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04xs57h96","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of 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