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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Molecular Microbiology; v. 122, n. 5, p. 10-pg., 2024-11-01.

Resumo

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)

• Processo FAPESP: 18/12896-2 - Avaliação do papel de proteases secretadas por leptospira na degradação e inativação de moléculas do hospedeiro
• Beneficiário: Angela Silva Barbosa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/22706-9 - Produção e caracterização da protease papalisina de Leptospira interrogans
• Beneficiário: Daniella dos Santos Courrol
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/12924-3 - Etiopatogênese da Leptospirose: contribuição do sistema complemento in vivo e in vitro para o controle da infecção e desencadeamento da resposta inflamatória tecidual: estudo de polimorfismos de genes do sistema complemento em pacientes com Leptospirose
• Beneficiário: Lourdes Isaac
• Modalidade de apoio: Auxílio à Pesquisa - Temático