The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components

Author(s)

Takahashi, M. B. ^{[1, 2]} ; Teixeira, A. F. ^[1] ; Alto, Nascimento ^[1]

Affiliation

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

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

• Document type: Journal article
• Source: VIRULENCE; v. 12, n. 1, p. 2798-2813, DEC 31 2021.
• Web of Science Citations: 0

Abstract

Leptospirosis is a globally prevalent zoonotic disease, and is caused by pathogenic spirochetes from the genus Leptospira. LipL21 and LipL41 are lipoproteins expressed strongly on the outer membrane of pathogenic Leptospira spp. Many studies have shown that both proteins are interesting targets for vaccines and diagnosis. However, their role in host-pathogen interactions remains underexplored. Therefore, we evaluated the capacity of LipL21 and LipL41 to bind with glycosaminoglycans (GAGs), the cell receptors and extracellular matrix, and plasma components by ELISA. Both proteins interacted with collagen IV, laminin, E-cadherin, and elastin dose-dependently. A broad-spectrum binding to plasma components was also observed. Only LipL21 interacted with all the GAG components tested, whereas LipL41 presented a concentration-dependent binding only for chondroitin 4 sulfate. Although, both proteins have the ability to interact with fibrinogen, only LipL21 inhibited fibrin clot formation partially. Both proteins exhibited a decrease in plasminogen binding in the presence of amino caproic acid (ACA), a competitive inhibitor of lysine residues, suggesting that their binding occurs via the kringle domains of plasminogen. LipL41, but not LipL21, was able to convert plasminogen to plasmin, and recruit plasminogen from normal human serum, suggesting that the interaction of this protein with plasminogen may occur in physiological conditions. This work provides the first report demonstrating the capacity of LipL21 and LipL41 to interact with a broad range of host components, highlighting their importance in host-Leptospira interactions. (AU)

• FAPESP's process: 17/26223-7 - Evaluation of functional role of Leptospira interrogans surface proteins as endothelial and epithelial cells receptors of the host
• Grantee: Maria Beatriz Takahashi
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 19/17488-2 - Advancing the understanding of pathogenesis and virulence of Leptospira interrogans through proteomics, structural, mutagenesis and immunological analyses
• Grantee: Ana Lucia Tabet Oller do Nascimento
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/00236-5 - Platelets at the interface of immunity, inflammation and hemostasis modulation in leptospirosis
• Grantee: Mônica Larucci Vieira
• Support Opportunities: Research Grants - Young Investigators Grants