The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author SIQUEIRA, Gabriela H.
TEIXEIRA, Aline F.
FERNANDES, Luis G.
SOUZA, Gisele O. de
KIRCHGATTER, Karin FMUSP-HC
ROMERO, Eliete C.
VASCONCELLOS, Silvio A.
VIEIRA, Monica L.
NASCIMENTO, Ana Lucia T. O.
dc.date.issued 2016
dc.identifier.citation PATHOGENS AND DISEASE, v.74, n.2, article ID UNSP ftv118, 11p, 2016
dc.identifier.issn 2049-632X
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/14598
dc.description.abstract Leptospirosis is a zoonosis caused by pathogenic Leptospira spp. In this study, we report that the recombinant proteins LIC10507, LIC10508 and LIC10509 are recognized by confirmed leptospirosis serum samples at both phases of the disease. The recombinant rLIC10508 and rLIC10507 are plasminogen (PLG)-binding proteins, capable of generating plasmin in the presence of a PLG activator. The proteins bind to PLG in a dose-dependent and saturable manner, fulfilling host-ligand interaction. Furthermore, rLIC10508 interacts with fibrinogen (Fg), plasma fibronectin and C4b binding protein (C4BP). The binding of rLIC10508 to Fg decreases the fibrin clotting in a thrombin-catalyzed reaction. The incubation with 4 mu M of protein promoted 40% inhibition upon clotting formation. C4BP bound to rLIC10508 retained its cofactor activity for factor I promoting the cleavage of C4b protein, which may reduce the membrane attack complex formation. Although these proteins have high amino acid sequence similarity, rLIC10508 is the most talented of the three, a behavior that might be explained by its unique putative 3D structure, whereas structures of rLIC10507 and rLIC10509 are very similar. Plasmin generation (rLIC10507 and rLIC10508), together with decreasing fibrin clot formation (rLIC10508) and impairment of the complement system (rLIC10508) may help the bacteria to overcome host defense, facilitating the infection process.
dc.description.sponsorship · FAPESP [12/23913-9]
· CNPq [302758/2013-5, 441449/2014-0]
· Fundacao Butantan, Brazil
· FAPESP (Brazil) [2014/03792-8, 2012/50523-7, 2014/18337-4, 2012/01797-7, 2012/24164-0]
dc.language.iso eng
dc.publisher OXFORD UNIV PRESS
dc.relation.ispartof Pathogens and Disease
dc.rights restrictedAccess
dc.subject Leptospira; leptospirosis; plasmin; fibrinogen; C4BP; host interactions
dc.subject.other complement regulator c4bp; in-vitro; endothelial-cells; binding protein; immune evasion; clot formation; pathogenesis; infection; surface; activation
dc.title The recombinant LIC10508 is a plasma fibronectin, plasminogen, fibrinogen and C4BP-binding protein of Leptospira interrogans
dc.type article
dc.rights.holder Copyright OXFORD UNIV PRESS
dc.description.group LIM/49
dc.identifier.doi 10.1093/femspd/ftv118
dc.identifier.pmid 26657108
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author KIRCHGATTER, Karin:IMT:
hcfmusp.author.external · SIQUEIRA, Gabriela H.:Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil
· TEIXEIRA, Aline F.:Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil; Univ Sao Paulo, ICB, Programa Posgrad Interunidades Biotecnol, Ave Prof Lineu Prestes 1730, BR-05503900 Sao Paulo, SP, Brazil
· FERNANDES, Luis G.:Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil; Univ Sao Paulo, ICB, Programa Posgrad Interunidades Biotecnol, Ave Prof Lineu Prestes 1730, BR-05503900 Sao Paulo, SP, Brazil
· SOUZA, Gisele O. de:Univ Sao Paulo, Fac Med Vet & Zootecnia, Lab Zoonoses Bacterianas VPS, Ave Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo, SP, Brazil
· ROMERO, Eliete C.:Adolfo Lutz Inst, Ctr Bacteriol, Ave Dr Arnaldo 355, BR-01246902 Sao Paulo, SP, Brazil
· VASCONCELLOS, Silvio A.:Univ Sao Paulo, Fac Med Vet & Zootecnia, Lab Zoonoses Bacterianas VPS, Ave Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo, SP, Brazil
· VIEIRA, Monica L.:Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil
· NASCIMENTO, Ana Lucia T. O.:Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP, Brazil; Univ Sao Paulo, ICB, Programa Posgrad Interunidades Biotecnol, Ave Prof Lineu Prestes 1730, BR-05503900 Sao Paulo, SP, Brazil
hcfmusp.origem.id WOS:000371929200007
hcfmusp.origem.id 2-s2.0-84992107193
hcfmusp.publisher.city OXFORD
hcfmusp.publisher.country ENGLAND
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dc.description.index MEDLINE
hcfmusp.citation.scopus 4
hcfmusp.citation.wos 3
hcfmusp.affiliation.country Brasil


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