Molecular, biochemical and immunological characterization of Amblyomma sculptum salivary protease inhibitors: from immunobiologics development to anti-tick strategies

• Grant number: 22/02742-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2022
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Entomology and Malacology of Parasites and Vectors
• Principal Investigator: Anderson de Sá Nunes
• Grantee: Anderson de Sá Nunes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Andréa Cristina Fogaça ; Eliane Virginia da Silva Esteves ; Lucas Tirloni ; Michail Kotsyfakis

Abstract

Among the tick species present in Brazil, those of the Amblyomma genus present the greatest abundance and distribution in the country. Amblyomma sculptum is endemic in the Southeast region and has capybaras, tapirs and horses as hosts, in addition to the potential to parasitize humans. This species is responsible for the transmission of the bacterium Rickettsia rickettsii, which causes Brazilian spotted fever, the most severe rickettsiosis known. Both hematophagous success and pathogen transmission by ticks are strongly dependent on the bioactive molecules present in their saliva. However, despite the relevance of Amblyomma sculptum in human and veterinary public health, studies evaluating the effects of its saliva and salivary components on the physiology of the vertebrate host are scarce. Previous successful experiences by our group that elucidated the role of saliva and salivary molecules from other tick species led us to investigate the role of Amblyomma sculptum saliva in the interactions with the vertebrate host. The present project represents a deepening of these studies, where we intend to determine the structural and biochemical targets of two protease inhibitors belonging to the most abundant families found in tick saliva (a Kunitz-type inhibitor and a cystatin) selected from the sialotranscriptome of Amblyomma sculptum. We will also dissect their mechanisms of action in the hemostatic and immune responses of mice, and test the usefulness of these molecules as immunobiologicals in experimental models of inflammatory/autoimmune diseases and as vaccines to protect against tick exposure. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARROS, RAFAEL DOS SANTOS; QUEIROZ, LUIZ ADRIANO DAMASCENO; ASSIS, JOSIANE BETIM DE; PANTOJA, KAMILLA COSTA; BUSTIA, SOFIA XAVIER; DE SOUSA, EMANUELLA SARMENTO ALHO; RODRIGUES, STEPHEN FERNANDES; AKAMINE, ELIANA HIROMI; SA-NUNES, ANDERSON; MARTINS, JOILSON O.. Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence. FRONTIERS IN IMMUNOLOGY, v. 15, p. 14-pg., 2024-03-07. (20/03175-0, 22/02742-3, 22/00482-4, 21/00310-6, 20/05439-4, 20/07212-7)