Leucine-rich repeat proteins of Leptospira interrogans that interact to host glycosaminoglycans and integrins

Autor(es)

Foltran, Bruno B. ; Teixeira, Aline F. ; Romero, Eliete C. ; Fernandes, Luis G. V. ; Nascimento, Ana L. T. O.

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 15, p. 18-pg., 2024-11-26.

Resumo

Pathogenic spirochaetes of the genus Leptospira are the etiological agents of leptospirosis, a zoonotic infection worldwide. The disease is considered an emerging and re-emerging threat due to global warming, followed by heavy rainfall and flooding when outbreaks of leptospirosis occur. Adhesion to host tissues is mediated by surface/extracellular proteins expressed by pathogens during infection. Leucine-rich repeat (LRR) domain-containing proteins seem to be important for the virulence of pathogenic Leptospira and their role has been recently examined. Here, we report the characterization of two LRR-proteins encoded by LIC11051 and LIC11505. They present 7 and 17 LRR motifs, respectively. LIC11051 was found mainly in the P1 subclade, whereas LIC11505 was identified with higher identity in subclade P1, but was also found in subclades P2, S1, and S2. The recombinant proteins were recognized by antibodies in leptospirosis serum samples, suggesting their expression during infection. rLIC11505 contains a broad spectrum of ligands, including GAG and integrin receptors, whereas rLIC11051 showed limited binding activity. The attachment of proteins to ligands was specific, dose-dependent, and saturable. Compared to their role in adhesion, both proteins were shown to be secreted, with the ability to reassociate with the bacteria. Taken together, our data suggested that LIC11051 and LIC11505 participate in leptospiral pathogenesis. To the best of our knowledge, this is the first report showing leptospiral LRR-proteins exhibiting GAG and integrin receptor-binding properties. (AU)

• Processo FAPESP: 22/16481-7 - Obtenção de mutantes de proteínas Leucine Rich Repeats (LRR) em Leptospira interrogans e avaliação fenotípica das interações patógeno-hospedeiro
• Beneficiário: Bruno Botega Foltran
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/06731-8 - Aplicação de CRISPR-interferência na elucidação da patogênese da leptospirose e desenvolvimento de novas estratégias para obtenção de mutantes knockout
• Beneficiário: Luis Guilherme Virgílio Fernandes
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/11541-0 - Avaliação do potencial vacinal de frações antigênicas obtidas em Leptospira interrogans serovar Copenhageni utilizando hamster como modelo animal
• Beneficiário: Aline Florencio Teixeira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado