Genomic analysis of Aspergillus cryptic species

• Grant number: 17/21983-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2018
• End date: November 30, 2021
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Renato Augusto Corrêa dos Santos
• Host 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.

Scientific publications

(6)

(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)

ZUVANOV, LUIZA; BASSO GARCIA, ANA LETYCIA; CORRER, FERNANDO HENRIQUE; BIZARRIA JR, RODOLFO; DA COSTA FILHO, AILTON PEREIRA; DA COSTA, ALISSON HAYASI; THOMAZ, ANDREA T.; MENDES PINHEIRO, ANA LUCIA; RIANO-PACHON, DIEGO MAURICIO; WINCK, FLAVIA VISCHI; et al. he experience of teaching introductory programming skills to bioscientists in Brazi. PLOS COMPUTATIONAL BIOLOGY, v. 17, n. 11, NOV 2021. (17/21983-3, 19/10727-1, 15/03541-8, 20/02084-0, 19/24412-2, 17/10373-0, 19/07526-4, 20/04437-8)

RIES, LAURE N. A.; PARDESHI, LAKHANSING; DONG, ZHICLIANG; TAN, KAELING; STEENWYK, JACOB L.; COLABARDINI, ANA CRISTINA; FERREIRA FILHO, JAIRE A.; DE CASTRO, PATRICIA A.; SILVA, LILIAN P.; PREITE, NYCOLAS W.; et al. The Aspergillus fumigatus transcription factor RglT is important for gliotoxin biosynthesis and self-protection, and virulence. PLOS PATHOGENS, v. 16, n. 7, JUL 2020. (17/14159-2, 17/21983-3, 18/25217-6, 17/07536-4, 17/01188-4, 13/50954-0, 14/00789-6, 13/07937-8, 16/07870-9, 19/09278-8, 16/03322-7)

CORREA DOS SANTOS, RENATO AUGUSTO; RIVERO-MENENDEZ, OLGA; STEENWYK, JACOB L.; MEAD, MATTHEW E.; GOLDMAN, GUSTAVO HENRIQUE; ALASTRUEY-IZQUIERDO, ANA; ROKAS, ANTONIS. Draft Genome Sequences of Four Aspergillus Section Fumigati Clinical Strains. MICROBIOLOGY RESOURCE ANNOUNCEMENTS, v. 9, n. 40, OCT 2020. (17/21983-3, 16/07870-9, 19/07526-4)

DOS SANTOS, RENATO AUGUSTO CORREA; MEAD, MATTHEW E.; STEENWYK, JACOB L.; RIVERO-MENENDEZ, OLGA; ALASTRUEY-IZQUIERDO, ANA; GOLDMAN, GUSTAVO HENRIQUE; ROKAS, ANTONIS. Examining Signatures of Natural Selection in Antifungal Resistance Genes Across Aspergillus Fungi. FRONTIERS IN FUNGAL BIOLOGY, v. 2, p. 12-pg., 2021-09-10. (17/21983-3, 16/07870-9, 19/07526-4)

STEENWYK, JACOB L.; MEAD, MATTHEW E.; DE CASTRO, PATRICIA ALVES; VALERO, CLARA; DAMASIO, ANDRE; DOS SANTOS, RENATO A. C.; LABELLA, ABIGAIL L.; LI, YUANNING; KNOWLES, SONJA L.; RAJA, HUZEFA A.; et al. Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus. MICROBIOLOGY SPECTRUM, v. 9, n. 1, SEP 2021. (19/07526-4, 17/21983-3, 18/00715-3)

DOS SANTOS, RENATO A. C.; STEENWYK, JACOB L.; RIVERO-MENENDEZ, OLGA; MEAD, MATTHEW E.; SILVA, LILIAN P.; BASTOS, RAFAEL W.; ALASTRUEY-LZQUIERDO, ANA; GOLDMAN, GUSTAVO H.; ROKAS, ANTONIS. Genomic and Phenotypic Heterogeneity of Clinical Isolates of the Human Pathogens Aspergillus fumigatus, Aspergillus lentulus, and Aspergillus fumigatiaffinis. FRONTIERS IN GENETICS, v. 11, MAY 12 2020. (17/21983-3, 16/07870-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Renato Augusto Corrêa dos. Análise genômica de espécies crípticas de Aspergillus. 2021. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.