Characterization of molecular mechanisms related to azoles resistance in Trichosporon asahii clinical isolates

• Grant number: 18/19347-4
• Support Opportunities: Scholarships abroad - Research
• Start date: September 01, 2019
• End date: August 31, 2020
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: João Nóbrega de Almeida Júnior
• Grantee: João Nóbrega de Almeida Júnior
• Host Investigator: David S. Perlin
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Hackensack Meridian Health, United States

Abstract

Trichosporon asahii is an emergent agent of invasive infection in immunocompromised hosts and patients with invasive disposals. Azoles are the best therapeutic approach for treating invasive trichosporonosis, but epidemiological and microbiological data obtained by the Brazilian Trichosporon Network documented T. asahii from deep-seated infections with high MICs against fluconazole (>32mg/L) e voriconazole (>2mg/L). The antifungal resistance mechanisms are not yet defined, and mutations in the genes related to the cell membrane ergosterol synthesis pathway, as well as efflux pumps, may be the possible resistance mechanisms. Recently, mutations in genes related to the DNA repair pathways were related to the emergence of a mutator phenotype in Candida glabrata and Cryptocococcus neoformans. This mutator phenotype is able to accumulate mutations and to exhibit a higher propensity to develop antifungal resistance. Thus, this study aims to investigate and to describe the antifungal resistance mechanisms in T. asahii clinical isolates, which includes investigation of mutations in genes related to the cell membrane ergosterol synthesis pathway, analysis of efflux pumps expression after azole exposure, and finally, mutations in the mismatch repair system genes and emergence mutator phenotypes. This project consolidates the partnership among the University of São Paulo, the Federal University of São Paulo, and the Center for Discovery and Innovation from the Hackensack Meridian Health Institute. (AU)

Scientific publications

(10)

(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)

ARASTEHFAR, AMIR; DE ALMEIDA JUNIOR, JOAO N.; PERLIN, DAVID S.; ILKIT, MACIT; BOEKHOUT, TEUN; COLOMBO, ARNALDO LOPES. Multidrug-resistant Trichosporon species: underestimated fungal pathogens posing imminent threats in clinical settings. CRITICAL REVIEWS IN MICROBIOLOGY, JUN 2021. (18/19347-4)

DE ALMEIDA JR, JOAO NOBREGA; FRANCISCO, ELAINE CRISTINA; RUIZ, ALEXIS HOLGUIN; CUELLAR, LUIS E.; AQUINO, VALERIO RODRIGUES; MENDES, ANA VERENA; QUEIROZ-TELLES, FLAVIO; SANTOS, DANIEL WAGNER; GUIMARAES, THAIS; CHAVES, GUILHERME MARANHAO; et al. Epidemiology, clinical aspects, outcomes and prognostic factors associated with Trichosporon fungaemia: results of an international multicentre study carried out at 23 medical centres. Journal of Antimicrobial Chemotherapy, v. 76, n. 7, p. 1907-1915, JUL 2021. (18/19347-4)

ROSSATO, LUANA; CARLESSE, FABIANNE; DE ALMEIDA, JOAO NOBREGA, JR.; KONTOYIANNIS, DIMITRIOS P.; COLOMBO, ARNALDO LOPES. How different is invasive fusariosis in pediatric patients than in adults? A systematic review. Current Opinion in Infectious Diseases, v. 34, n. 6, p. 8-pg., 2021-12-01. (18/19347-4, 17/02203-7)

THOMAZ, DANILO Y.; DE ALMEIDA, JOAO N.; SEJAS, ODELI N. E.; DEL NEGRO, GILDA M. B.; CARVALHO, GABRIELLE O. M. H.; GIMENES, VIVIANE M. F.; DE SOUZA, MARIA EMILIA B.; ARASTEHFAR, AMIR; CAMARGO, CARLOS H.; MOTTA, ADRIANA L.; et al. Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center. JOURNAL OF FUNGI, v. 7, n. 4, APR 2021. (19/17851-0, 17/00231-3, 18/19347-4, 16/08730-6)

LIMA, RICARDO; RIBEIRO, FELIPE C.; COLOMBO, ARNALDO L.; DE ALMEIDA JR, JOAO N.. The emerging threat antifungal-resistant Candida tropicalis in humans, animals, and environment. FRONTIERS IN FUNGAL BIOLOGY, v. 3, p. 11-pg., 2022-08-15. (17/02203-7, 18/19347-4)

DE ALMEIDA, JR., JOAO N.; FRANCISCO, ELAINE C.; HAGEN, FERRY; BRANDAO, IGOR B.; PEREIRA, FELICIDADE M.; PRESTA DIAS, PEDRO H.; DE MIRANDA COSTA, MAGDA M.; DE SOUZA JORDAO, REGIANE T.; DE GROOT, THEUN; COLOMBO, ARNALDO L.. Emergence of Candida auris in Brazil in a COVID-19 Intensive Care Unit. JOURNAL OF FUNGI, v. 7, n. 3, MAR 2021. (18/19347-4, 17/02203-7)

DE ALMEIDA JR, JOAO NOBREGA; MORENO, LIS; FRANCISCO, ELAINE CRISTINA; MARQUES, GABRIELA NORONHA; MENDES, ANA VERENA; BARBERINO, MARIA GORETH; COLOMBO, ARNALDO LOPES. Trichosporon asahii superinfections in critically ill COVID-19 patients overexposed to antimicrobials and corticosteroids. MYCOSES, v. 64, n. 8, p. 817-822, AUG 2021. (18/19347-4)

ARASTEHFAR, AMIR; DE ALMEIDA JUNIOR, JOAO N.; PERLIN, DAVID S.; ILKIT, MACIT; BOEKHOUT, TEUN; COLOMBO, ARNALDO LOPES. Multidrug-resistant Trichosporon species: underestimated fungal pathogens posing imminent threats in clinical settings. CRITICAL REVIEWS IN MICROBIOLOGY, v. 47, n. 6, p. 679-698, NOV 2 2021. (18/19347-4)

THOMAZ, DANILO Y.; DEL NEGRO, GILDA M. B.; RIBEIRO, LEIDIANE B.; DA SILVA, MIRIAN; CARVALHO, GABRIELLE O. M. H.; CAMARGO, CARLOS H.; DE ALMEIDA, JOAO N.; MOTTA, ADRIANA L.; SICILIANO, RINALDO F.; SEJAS, ODELI N. E.; et al. A Brazilian Inter-Hospital Candidemia Outbreak Caused by Fluconazole-Resistant Candida parapsilosis in the COVID-19 Era. JOURNAL OF FUNGI, v. 8, n. 2, p. 8-pg., 2022-02-01. (18/19347-4, 18/15491-3, 21/00871-8, 19/17851-0)

DE ALMEIDA JR, JOAO NOBREGA; JIMENEZ-ORTIGOSA, CRISTINA; FRANCISCO, ELAINE CRISTINA; COLOMBO, ARNALDO L. L.; PERLIN, DAVID S. S.. ERG11 Analysis among Clinical Isolates of Trichosporon asahii with Different Azole Susceptibility Profiles. Antimicrobial Agents and Chemotherapy, v. 66, n. 12, p. 5-pg., 2022-11-14. (18/19347-4)