LIC12254 Is a Leptospiral Protein That Interacts with Integrins via the RGD Motif

Author(s)

Cavenague, Maria F. F. ; Teixeira, Aline F. F. ; Fernandes, Luis G. V. ; Nascimento, Ana L. T. O.

• Document type: Journal article
• Source: TROPICAL MEDICINE AND INFECTIOUS DISEASE; v. 8, n. 5, p. 15-pg., 2023-04-26.

Abstract

Pathogenic leptospires can bind to receptors on mammalian cells such as cadherins and integrins. Leptospira effectively adheres to cells, overcomes host barriers and spreads into the bloodstream, reaching internal target organs such as the lungs, liver and kidneys. Several microorganisms produce proteins that act as ligands of integrins through the RGD motif. Here, we characterized a leptospiral RGD-containing protein encoded by the gene lic12254. In silico analysis of pathogenic, intermediate and saprophytic species showed that LIC12254 is highly conserved among pathogenic species,and is unique in presenting the RGD motif. The LIC12254-coding sequence is greatly expressed in the virulent Leptospira interrogans L1-130 strain compared with the culture-attenuated L. interrogans M20 strain. We also showed that the recombinant protein rLIC12254 binds to alpha V beta 8 and a8 human integrins most likely via the RGD motif. These interactions are dose-dependent and saturable, a typical property of receptor-ligand interactions. The binding of the recombinant protein lacking this motif-rLIC12254 Delta RAA-to alpha V beta 8 was almost totally abolished, while that with the a8 human integrin was decreased by 65%. Taken together, these results suggest that this putative outer membrane protein interacts with integrins via the RGD domain and may play a key role in leptospirosis pathogenesis. (AU)

• FAPESP's process: 18/08131-0 - Heterologous expression of the gene LIC13259 in the saprophyte Leptospira biflexa and their acquisition capacity to evade the human immune system
• Grantee: Maria Fernanda Cavenague Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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: 16/11541-0 - Evaluation of the vaccine potential of antigenic fractions obtained in Leptospira interrogans serovar Copenhageni using hamsters as an animal model
• Grantee: Aline Florencio Teixeira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• 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