Characterization of transcriptional programs important for resistance and tolerance to Caspofungin

• Grant number: 22/08642-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2022
• Effective date (End): August 31, 2024
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Iran Malavazi
• Grantee: Jonatas Erick Maimoni Campanella
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 21/04977-5 - The identification of new pathways and compounds that can enhance caspofungin activity against Aspergillus fumigatus, AP.TEM

Abstract

Invasive Pulmonary Aspergillosis (IPA), mainly caused by the saprophyte Aspergillus fumigatus, is a clinical condition associated with high mortality rates depending on the immunological status of the host. Caspofungin (CSP), yet the second choice of therapy, is an important echinocandin for the treatment of IPA, targeting the fungal cell wall, promoting growth inhibition but favoring an effect known as Caspofungin Paradoxical Effect (CPE). Previous results in our laboratory have shown that several proteins involved in thermotolerance, cell wall integrity, fatty acids metabolism, and virulence also affect the extent of A. fumigatus CPE. This group of proteins includes enzymes involved in lipid biosynthesis and oxylipins, MAP kinases, chaperones, and multiple transcription factors. Here, our goal is to study the functional and transcriptional roles of these proteins in the susceptibility of the fungus to different drugs and drug associations, including Caspofungin. To this end, we will combine different molecular techniques, such as gene and protein expression, RNA-seq, and ChIP-seq. The outcome of these combined analyses will delineate the overall regulatory network for CSP response providing important insights into the regulation of CSP resistance and tolerance (CPE) in A. fumigatus. (AU)