Multifunctional and Redundant Roles of Leptospira interrogans Proteins in Bacterial-Adhesion and fibrin clotting inhibition

Author(s)

Pereira, Priscila R. M. ^{[1, 2]} ; Fernandes, Luis G. V. ^{[1, 2]} ; de Souza, Gisele O. ^[3] ; Vasconcellos, Silvio A. ^[3] ; Heinemann, Marcos B. ^[3] ; Romero, Eliete C. ^[4] ; Nascimento, Ana L. T. O. ^{[1, 2]}

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, Ave Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Programa Posgrad Interunidades Biotecnol, Ave Prof Lineu Prestes 1730, BR-05508900 Sao Paulo, SP - Brazil

^[3] 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

^[4] Adolfo Lutz Inst, Ctr Bacteriol, Ave Dr Arnaldo 355, BR-01246902 Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY; v. 307, n. 6, p. 297-310, SEP 2017.
• Web of Science Citations: 6

Abstract

Pathogenic Leptopira is the etiological agent of leptospirosis, the most widespread zoonotic infection in the world. The disease represents a major public health problem, especially in tropical countries. The present work focused on two hypothetical proteins of unknown function, encoded by the genes LIC13059 and LIC10879, and predicted to be surface-exposed proteins. The genes were cloned and the proteins expressed using E. colt as a host system. We report that the recombinant proteins interacted with extracellular matrix (ECM) laminin, in a dose dependent fashion and are novel potential adhesins. The recombinant proteins were called Lsa25.6 (rLIC13059) and Lsal6 (rLIC10879), for Leptospiral surface adhesins, followed by the respective molecular masses. The proteins attached to plasminogen (PLG), generating plasmin, in the presence of PLG-activator uPA. Both proteins bind to fibrinogen (Fg), but only Lsa25.6 inhibited fibrin clotting by thrombin-catalyzed reaction. Moreover, Lsal6 interacts with the mammalian cell receptor E-cadherin, and could contribute to bacterial attachment to epithelial cells. The proteins were recognized by confirmed leptospirosis serum samples, suggesting that they are expressed during infection. The corresponding leptospiral proteins are surface exposed based on proteinase K accessibility assay, being LIC10879 most probably exposed in its dimer form. The data of this study extend the spectrum of surface-exposed proteins of L. interrogans and indicate a possible role of the originally annotated hypothetical proteins in infection processes. (AU)

• FAPESP's process: 15/02590-5 - Immunological and functional characterization of two predict lipoproteins of Leptospira interrogans expressed in the host Escherichia coli
• Grantee: Priscila Romero Mazzini Pereira
• Support Opportunities: Scholarships in Brazil - Master
• 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
• FAPESP's process: 12/23913-9 - Indentification and characterization of proteins of Leptospira interrogans involved in host-pathogen interactions
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/24164-0 - Characterization of the interaction of Leptospira interrogans with prothrombin/thrombin system and possible implications in virulence
• Grantee: Luis Guilherme Virgílio Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate