The interaction of two novel putative proteins of Leptospira interrogans with E-cadherin, plasminogen and complement components with potential role in bacterial infection

Author(s)

Kochi, Leandro T. ^{[1, 2]} ; Fernandes, V, Luis G. ; Souza, Gisele O. ^[3] ; Vasconcellos, Silvio A. ^[3] ; Heinemann, Marcos B. ^[3] ; Romero, Eliete C. ^[4] ; Kirchgatter, Karin ^[5] ; Nascimento, Ana L. T. O. ^[6]

Affiliation

^[1] Inst Butantan, Lab Especial Desenvolvimento Vacinas, Sao Paulo - Brazil

^[2] Inst Ciencias Biomed, Programa Posgrad Interunidades Biotecnol, Sao Paulo - Brazil

^[3] Fac Med Vet & Zootecnia, Lab Zoonoses Bacterianas, Sao Paulo - Brazil

^[4] Adolfo Lutz Inst, Ctr Bacteriol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Nucleo Estudos Malaria, Superintendencia Controle Endemias SUCEN IMT SP, Sao Paulo - Brazil

^[6] Fernandes, Luis G., V, Inst Butantan, Lab Especial Desenvolvimento Vacinas, Sao Paulo - Brazil

• Document type: Journal article
• Source: VIRULENCE; v. 10, n. 1, p. 734-753, JAN 1 2019.
• Web of Science Citations: 0

Abstract

Leptospirosis is a worldwide zoonosis caused by pathogenic species of Leptospira. Leptospires are able to adhere to exposed extracellular matrix in injured tissues and, once in the bloodstream, can survive the attack of the immune system and spread to colonize target organs. In this work, we report that two novel putative proteins, coded by the genes LIC11711 and LIC12587 of L. interrogans serovar Copenhageni are conserved among pathogenic strains, and probably exposed in the bacterial surface. Soluble recombinant proteins were expressed in Escherichia coli, purified and characterized. Both recombinant proteins bound to laminin and E-cadherin, suggesting an initial adhesion function in host epithelial cells. The recombinant protein LIC11711 (rLIC11711) was able to capture plasminogen (PLG) from normal human serum and convert to enzymatically active plasmin (PLA), in the presence of PLG activator. rLIC12587 (recombinant protein LIC12587) displayed a dose dependent and saturable interaction with components C7, C8, and C9 of the complement system, reducing the bactericidal effect of the complement. Binding to C9 may have consequences such as C9 polymerization inhibition, interfering with the membrane attack complex formation. Blocking LIC11711 and LIC12587 on bacterial cells by the respective antiserum reduced leptospiral cell viability when exposed to normal human serum (NHS). Both recombinant proteins could be recognized by serum samples of confirmed leptospirosis, but not of unrelated diseases, suggesting that the native proteins are immunogenic and expressed during leptospirosis. Taken together, our data suggest that these proteins may have a role in leptospiral pathogenesis, participating in immune evasion strategies. (AU)

• FAPESP's process: 16/01384-5 - Evaluation of the functional role of two Leptospira interrogans proteins in the adhesion process of the pathogen to the host
• Grantee: Leandro Toshio Kochi
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/06731-8 - Application of CRISPR-interference for elucidating leptospirosis pathogenesis and development of novel strategies for knockout mutant's obtainment
• Grantee: Luis Guilherme Virgílio Fernandes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50981-0 - Search for surface proteins among the genome sequences of Leptospira interrogans: functional and immunological characterization to understanding mechanisms involved in the bacterial pathogenesis
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Support Opportunities: Research Projects - Thematic Grants