Obtaining and characterizing titan and persister cells in Cryptococcus: cellular plasticity in different microenvironments

• Grant number: 24/14647-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: December 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Kelly Ishida
• Grantee: Nathalia Cristina Lopes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cryptococcus neoformans and Cryptococcus gattii complexes are responsible for causing cryptococcosis, a serious systemic and opportunistic infection in human host. Initially, the infection occurs in the lungs; however, the microorganism has a high tropism for the Central Nervous System (CNS) and, in severe cases of the disease, progresses to cryptococcal meningitis. The progression of the disease is due to several factors that are still poorly understood, highlighting the adaptive capacity of the microorganism, such as morphological alteration in order to resist aggressive stimuli, such as enlargement of the polysaccharide capsule, production of titans cells and microcells. In addition to these morphotypes, persistent cell subpopulations in biofilms are capable of resisting high concentrations of antifungals. In this regard, the present project aims to obtain and characterize the titans and persistent cells of C. neoformans and C. gattii and evaluate cellular alterations subjected to different microenvironments. In this sense, both cell types will be challenged with stress and antifungal agents to evaluate the cellular plasticity of Cryptococcus in addition to associating the tolerance and survival mechanisms with the autophagy.