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Impact of paracoccin overexpression in the biology and virulence of Paracoccidioides spp. conidia

Grant number: 17/06251-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): December 01, 2017
Effective date (End): January 31, 2021
Field of knowledge:Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
Principal Investigator:Maria Cristina Roque Antunes Barreira
Grantee:Nayla de Souza Pitangui
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/04088-0 - Lectin from pathogens, AP.TEM

Abstract

Dimorphic fungi from the "complex" Paracoccidioides cause paracoccidioidomycosis (PCM), a primarily pulmonary and potentially disseminate disease with high prevalence and morbidity in Latin America. Infection begins when humans inhale conidia (infectious fungal form), while the development of disease depends fundamentally on the conversion, in the pulmonary alveoli, of conidia in yeast (pathogenic forms of the fungus) and host immune response. Few fungal components display immunomodulatory properties. It is the case of the bifunctional protein paracoccin (PCN), endowed with lectin activity (toward N-acetyl glucosamine monomers or polymers) and enzymatic activity (chitinase). PCN immunomodulatory activities were demonstrated in vitro by the stimulus of macrophages to M1-polarization and production of pro-inflammatory mediators (such as IL-12). In vivo, PCN administration to mice infected with P. brasiliensis confers protection against the fungus, associated with Th1 immunity. Concerning the role played on fungal biology, PCN expression is five times higher in hyphae than in yeasts; in addition, PCN was detected in both morphotypes prominently in the fungal growth regions. The idea that PCN acts on fungal biology was reinforced by the inhibition of yeasts growth when anti-PCN antibodies were added to the fungal cultures, as well as by transition blockage of transformed fungi for PCN expression. The objective of this proposal is to evaluate the effect of PCN overexpression by P. brasiliensis and P. lutzii conidia, through the examination of their transition to yeasts and repercussions on the mice infection with conidia of transformed fungus. Alternatively, we will use the Galleria mellonella infection model. The study should contribute to elucidate factors determining the survival, growth and transitional capacity of the fungi, as well as the pathogenesis of the mycosis caused by them. (AU)