Characterization of mitogenomes of Aspergillus fumigatus populations with strains resistant and susceptible to antifungal drugs

• Grant number: 23/00206-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2023
• End date: May 31, 2026
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Endrews Delbaje
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , 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

It is increasingly observed that the role of the fungal mitochondria goes far beyond energy metabolism. These organelles have been associated with cell differentiation, regulation of hyphal and biofilm growth, drug resistance and virulence. Despite this, the role of the mitochondria of Aspergillus fumigatus, the main pulmonary fungus worldwide, in drug resistance still needs to be clarified. Furthermore, there is a lack of a detailed genomic study of mitochondrial sequence variations intraspecifically and in relation to resistant and susceptible populations of A. fumigatus to drugs. Currently, the main treatment against A. fumigatus infections is the administration of azole antifungal agents, and caspofungin echinocandin has been an alternative used as a second line of treatment. Within this context, a broad set of public sequencing data from different countries will be analyzed, to study the mitochondrial sequences from populations of A. fumigatus sensitive and resistant to azoles. Furthermore, published mitochondrial sequences of A. fumigatus strains that showed different susceptibility to caspofungin will be analyzed. For this, mitogenomes will be assembled and annotated for pan-genome analyses, analysis of single nucleotide polymorphisms, population phylogenies, in addition to other comparative and population structure analyzes that will be carried out. This work is expected to obtain information that will allow inferences about the mitochondrial evolution of an important clinical species, in addition to testing the hypothesis that there is a relationship between mitochondrial genetic characteristics that impact the resistance of A. fumigatus to antifungal drugs.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DELBAJE, ENDREWS; DE CASTRO, PATRICIA ALVES; CALISE, DANTE G.; MENGYAO, NIU; HORTA, MARIA AUGUSTA CRIVELENTE; AKIYAMA, DANIEL YURI; PONTES, JOAO GUILHERME; FILL, TAICIA; KNIEMEYER, OLAF; KRUGER, THOMAS; et al. The Influence of Aspergillus fumigatus Fatty Acid Oxygenases PpoA and PpoC on Caspofungin Susceptibility. JOURNAL OF FUNGI, v. 10, n. 11, p. 23-pg., 2024-11-01. (23/00206-0, 22/02992-0, 21/04977-5)

DOS REIS, THAILA FERNANDA; DELBAJE, ENDREWS; PINZAN, CAMILA FIGUEIREDO; BASTOS, RAFAEL; ACKLOO, SUZANNE; FALLAH, SARA; LAFLAMME, BRADLEY; ROBBINS, NICOLE; COWEN, LEAH E.; GOLDMAN, GUSTAVO H.. The GPCR antagonist PPTN synergizes with caspofungin providing increased fungicidal activity against Aspergillus fumigatus. MICROBIOLOGY SPECTRUM, v. N/A, p. 22-pg., 2025-03-17. (21/04977-5, 23/00206-0)

RINKER, DAVID C.; SAUTERS, THOMAS J. C.; STEFFEN, KARIN; GUMILANG, ADIYANTARA; RAJA, HUZEFA A.; RANGEL-GRIMALDO, MANUEL; PINZAN, CAMILA FIGUEIREDO; DE CASTRO, PATRICIA ALVES; DOS REIS, THAILA FERNANDA; DELBAJE, ENDREWS; et al. Strain heterogeneity in a non-pathogenic Aspergillus fungus highlights factors associated with virulence. COMMUNICATIONS BIOLOGY, v. 7, n. 1, p. 16-pg., 2024-09-04. (23/00206-0, 21/04977-5)