Evaluation of vacuolar alpha-mannosidase from Paracoccidioides brasiliensis as a therapeutic vaccine against experimental paracoccidioidomycosis in mice

• Grant number: 21/01528-5
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ademilson Panunto-Castelo
• Grantee: Ademilson Panunto-Castelo
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Paracoccidioidomycosis (PCM), a systemic mycosis caused by thermally dimorphic fungi from the genus Paracoccidioides, is endemic in Latin American countries and a public health problem in Brazil, which has the most cases of the disease. Different research groups have been searching for Paracoccidioides antigens to be used in diagnostic assays or prophylactic or therapeutic vaccines. In preliminary studies, our group identified the presence of a vacuolar alpha-mannosidase and its enzymatic activity in the supernatants from the cultures of P. brasiliensis Pb18 strain yeasts. We determined that the mRNA expression of this alpha-mannosidase in strains with different degrees of virulence was significantly higher in yeast than in mycelium and higher in virulent strain yeasts than in avirulent ones. The current project aims to evaluate the recombinant P. brasiliensis vacuolar alpha-mannosidase and its mRNA as therapy for PCM in a preclinical study in mice. This evaluation will also be carried out in association with drug therapy to improve the resolution of P. brasiliensis infections. Additionally, gene expression of alpha-mannosidase in yeasts obtained from infected animals at different times will be analyzed. This study may open perspectives on the use of a new therapeutic agent in PCM. (AU)