Amblyostatin-1, the first salivary cystatin from Amblyomma sculptum: biochemical targets, biological activity and potential use as a vaccine and immunobiological.

• Grant number: 22/07724-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2022
• End date: November 30, 2024
• Field of knowledge: Biological Sciences - Parasitology - Entomology and Malacology of Parasites and Vectors
• Principal Investigator: Anderson de Sá Nunes
• Grantee: Wilson Santos Molari
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 23/07831-7 - Amblyostatin-1, the first salivary cystatin from Amblyomma sculptum: biochemical targets, biological activity and potential use as a vaccine and immunobiological, BE.EP.MS

Abstract

Amblyomma spp. include the ticks with the largest abundance and distribution in Brazil. More specifically, Amblyomma sculptum, a species endemic to the southeast region, is an important parasite of several vertebrates, including humans. These ticks have high clinical relevance due to the transmission of pathogens such as Rickettsia rickettsii, a bacterium that causes Brazilian spotted fever, a disease with a high lethality rate. This transmission is facilitated by the presence of bioactive molecules present in the saliva of these ticks that are secreted during blood feeding. Some of these molecules have demonstrated modulatory activities on the host's hemostatic and immune responses at the cellular and biochemical levels to ensure that tick feeding successfully occurs and to prevent vertebrate rejection. These functions reveal the potential use of these molecules for the development of therapies to treat clinical conditions characterized by exacerbation of immune responses. Knowing the biological activities of salivary protease inhibitors from other tick species, the present work proposes to characterize the first cystatin of A. sculptum, named Amblyostatin-1, whose transcript was recently identified in the sialotranscriptome of the species. To this end, we aim to determine the three-dimensional structure of this inhibitor, to determine the structural and biochemical targets of the molecule, and to evaluate its activities by using in vitro experimental models of coagulation and cell culture (lymphocytes, macrophages, neutrophils and dendritic cells). Finally, we propose to evaluate the action of this molecule as an immunobiological agent in experimental models of inflammatory/autoimmune disease and to test its potential for the development of vaccines against ticks.