| Grant number: | 17/14159-2 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | November 01, 2017 |
| End date: | June 30, 2020 |
| Field of knowledge: | Biological Sciences - Microbiology - Applied Microbiology |
| Principal Investigator: | Laure Nicolas Annick Ries |
| Grantee: | Laure Nicolas Annick Ries |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
| Associated researchers: | Roberto do Nascimento Silva |
| Associated research grant(s): | 19/16291-0 - Identification of Aspergillus fumigatus protein kinases and phosphatases important for the anti-fungal drug response, AP.R SPRINT |
| Associated scholarship(s): | 18/01475-6 - The role of lactose and acetate metabolism in Aspergillus fumigatus virulence, BP.JP |
Abstract
Aspergillus fumigatus is a prominent opportunistic human fungal pathogen, that can cause a range of diseases, whose severity depends on the underlying disturbance in the host immune system. A. fumigatus possesses a range of virulence factors that determine its pathogenicity and allow successful colonisation of the host. Nutrient acquisition and subsequent metabolic processes are essential for initial colonisation and promoting fungal survival within the human host. The acquisition of essential minerals such as iron, zinc, and copper are essential for A. fumigatus pathogenicity, whereas little information exists on carbon source utilisation during infection, although they are required in large quantities to sustain biosynthetic processes. Furthermore, growth on a given carbon source has been shown to affect cell wall composition, another important virulence factor, therefore altering the solicited immune response and susceptibility to antifungal drugs. The main carbon sources encountered by A. fumigatus during infection are glucose, lactate and acetate, whose availability depends on the host niche and inflammation status. Whereas glucose metabolism and -related Carbon Catabolite Repression (CCR) have been studied in A. fumigatus, virtually nothing is known about lactate and acetate utilisation, although the genome encodes all components required for the uptake and subsequent metabolism of these carbon sources. This project therefore proposes to thoroughly investigate a role of lactate and acetate utilisation in A. fumigatus virulence. This work will start by identifying genes, via RNA sequencing, which are involved in lactate and acetate utilisation. Deletion strains will be generated for the identified genes and phenotypic characterisation, phagocytosis and virulence assays will be carried out for the same strains. In addition, metabolic flexibility analysis and metabolite analysis will be carried out to determine changes in metabolic pathways when grown in the presence of lactate and acetate and compared to glucose-grown cells. Furthermore, this project aims at determining differences in the composition of the cell wall in the presence of glucose, lactate and acetate and correlate this with increased susceptibility or resistance to antifungal agents and extracellular stresses. This project is expected to generate novel data which will further contribute to elucidating the A. fumigatus-mediated process of infection, therefore providing a relatively new and uncharacterised angle on A. fumigatus infection biology which could prove useful for laying a basis for a better comprehension of the disease and the possible development of novel and/or more efficient antifungal agents. (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |