Resistance to antifungals in Aspergillus spp. isolated from atmospheric air related to the Clinical Hospital of the Botucatu Medical School

• Grant number: 24/05008-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: October 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Marcia de Souza Carvalho Melhem
• Grantee: Daniely Yukimi Yamada Medeiros Alves
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Aspergillosis is a disease caused by fungi of the genus Aspergillus spp. The high mortality rates of this infection are associated with therapeutic failure with antifungal drugs, the condition of severe immunosuppression seen in a large number of patients and/or the development of resistance of the etiological agent. The project aims to investigate a mechanism of resistance, through overexpression of membrane proteins known as efflux pumps, in isolates of Aspergillus fumigatus and Aspergillus flavus. Susceptibility assessment will be carried out using the EUCAST screening method, followed by the minimum inhibitory concentration (MIC), following the microdilution methodology defined by the European EUCAST committee. 8 groups of 15 isolates of each species, resistant/susceptible/non-wild type/wild type to azoles and echinocandins, recovered from atmospheric air, internal and adjacent to the teaching hospital, will be evaluated. For susceptibility classification, the clinical cut-off points and, in their absence, the epidemiological cut-off points (ECOFFs) for two classes of drugs will be used: azoles (isavuconazole, itraconazole, posaconazole, voriconazole) and echinocandins. Overexpression of efflux pumps will be investigated by real-time quantitative polymerase chain reaction (RT-qPCR) analyzed using the cycle threshold (CT) method. If the role of efflux pumps in the resistant strains of Aspergillus spp. is elucidated, new targets to contain the spread of these agents could be studied for the development of new drugs and, in Brazil, it could stimulate new studies on the use of efflux pumps.