A Review on Host-Leptospira Interactions: What We Know and Future Expectations

Author(s)

Daroz, Brenda B. ; Fernandes, Luis G. V. ; Cavenague, Maria F. ; Kochi, Leandro T. ; Passalia, Felipe J. ; Takahashi, Maria B. ; Nascimento Filho, Edson G. ; Teixeira, Aline F. ; Nascimento, Ana L. T. O.

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 11, p. 13-pg., 2021-11-25.

Abstract

Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation. (AU)

• FAPESP's process: 18/06201-1 - Identification of virulence factors of Leptospira interrogans through comparative proteomics analysis
• Grantee: Edson Galdino Do Nascimento Filho
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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: 17/01102-2 - Biochemical and immunological evaluation of hypothetical surface proteins of Leptospira interrogans
• Grantee: Felipe José Passalia
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• 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: 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: 18/09652-4 - Evaluation of the interaction of Leptospira interrogans proteins with host components by constructing recombinant Leptospira biflexa
• Grantee: Leandro Toshio Kochi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/21959-8 - Evaluation of the functional role of HtrA-like proteins present in pathogenic strains by creating mutants of Leptospira biflexa and Leptospira interrogans
• Grantee: Brenda Daroz
• 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: 17/06731-8 - 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