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Genomic analysis of Aspergillus cryptic species

Grant number: 17/21983-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2018
Status:Discontinued
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Gustavo Henrique Goldman
Grantee:Renato Augusto Corrêa dos Santos
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):19/07526-4 - Genetic variation of secondary metabolite gene clusters in clinical isolates of cryptic species in the Aspergillus fumigatus complex (section Fumigati ), BE.EP.DR

Abstract

Aspergillus is a genus of industrially important filamentous fungi, employed for production of acids, enzymes, anticancer agents and secondary metabolites. These fungi, however, are also important because of their impact on human health. Aspergillus fumigatus, a ubiquitous environmental and air-borne pathogen, is the causative agent of Invasive Aspergillosis (IA), the most common opportunistic mould causing pulmonary infection. A. nidulans, a reference organism, has also been reported infecting immunocompromised patients, in particular with Chronic Granulomatous Disease (CGD). The increased resistance to the few antifungal drugs available, such as azoles and echinocandins, is of worldwide concern. In addition to these two species, cryptic species that are morphologically indistinguishable to either A. fumigatus or A. nidulans but which are genetically different (and can be distinguished using molecular methods) have been reported in clinical cases. The most notable example of such cryptic species is A. lentulus, for which increased drug resistance was already observed. Whole-Genome Sequencing (WGS) studies can be used for the genotypic characterization of fungi and to provide insights into their reproductive modes, either sexual, asexual or parasexual. Moreover, they can be helpful for characterization of ploidy changes, aneuploidy, hybridizations, and loss of heterozygosity. Despite extensive genomic analyses of species in the genus, no study has been published that included genomes of cryptic Aspergillus species. Our group previously characterized A. nidulans clinical isolates that showed different ploidy and their genomic sequence revealed low to medium (30 to 75%) mapping rates to the A. nidulans A4 reference genome, suggesting they could be possible hybrids. This project aims to characterize the genomes of cryptic Aspergillus species isolated from environmental and clinical samples in several regions of the world, and for which EUCAST (The European Committee on Antimicrobial Susceptibility Testing) method has been used to characterize their antifungal resistance. In particular, we will look for i) genes involved in sexual reproduction, ii) possible genetic events such as ploidy changes, hybridization, and loss of heterozygosity, and iii) genes previously characterized to be involved in antifungal resistance. We expect that genomic characterization of cryptic species will provide information whether they are true species or results of interspecies hybridization events. Moreover, we expect the results will provide a better genomic characterization that will be helpful for cryptic species differentiation and important for clinical guidance in therapy.