Leptospira Leptolysin Contributes to Serum Resistance but Is Not Essential for Acute Infection

Author(s)

Courrol, Daniella dos Santos ; Santos, Cassia Moreira ; Chura-Chambi, Rosa Maria ; Morganti, Ligia ; Avelar, Katia Eliane Santos ; Maia, Fernanda de Moraes ; Rodrigues-da-Silva, Rodrigo Nunes ; Wunder, Elsio Augusto ; Barbosa, Angela Silva

• Document type: Journal article
• Source: Molecular Microbiology; v. 122, n. 5, p. 10-pg., 2024-11-01.

Abstract

Previous in vitro works focusing on virulence determinants of the spirochete Leptospira implicated metalloproteinases as putative contributing factors to the pathogenicity of these bacteria. Those proteins have the capacity to degrade extracellular matrix components (ECM) and proteins of host's innate immunity, notably effectors of the complement system. In this study, we gained further knowledge on the role of leptolysin, one of the leptospiral-secreted metalloproteinases, previously described as having a broad substrate specificity. We demonstrated that a proportion of human patients with mild leptospirosis evaluated in the current study produced antibodies that recognize leptolysin, thus indicating that the protease is expressed during host infection. Using recombinant protein and a knockout mutant strain, Manilae leptolysin-, we determined that leptolysin contributes to Leptospira interrogans serum resistance in vitro, likely by proteolysis of complement molecules of the alternative, the classical, the lectin, and the terminal pathways. Furthermore, in a hamster model of infection, the mutant strain retained virulence; however, infected animals had lower bacterial loads in their kidneys. Further studies are necessary to better understand the role and potential redundancy of metalloproteinases on the pathogenicity of this important neglected disease. (AU)

• FAPESP's process: 18/12896-2 - ROLE OF PROTEASES SECRETED BY LEPTOSPIRA IN THE DEGRADATION AND INACTIVATION OF HOST MOLECULES
• Grantee: Angela Silva Barbosa
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/22706-9 - Production and characterization of the protease pappalysin from Leptospira interrogans
• Grantee: Daniella dos Santos Courrol
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 17/12924-3 - Etiopathogenesis of Leptospirosis: contribution of the complement system for the control of infection in vivo and in vitro and inflammatory response: identification of gene polymorphisms of the complement system in Leptospirosis patients
• Grantee: Lourdes Isaac
• Support Opportunities: Research Projects - Thematic Grants