Multidisciplinary and international network to characterize microbiological aspects and natural history of invasive fungal infections due Candida spp

• Grant number: 17/02203-7
• Support Opportunities: Research Projects - Thematic Grants
• Duration: November 01, 2017 - October 31, 2023
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Arnaldo Lopes Colombo
• Grantee: Arnaldo Lopes Colombo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Analy Salles de Azevedo Melo ; Jacques Franciscus Meis ; João Nóbrega de Almeida Júnior ; Marcio Luiz Moore Nucci
• Associated scholarship(s): 22/01293-0 - Evaluation of molecular mechanisms of resistance of Candida tropicalis in blood culture samples from 3 Latin America countries, BP.TT; 21/00527-5 - Mechanisms of virulence and pathogenicity expressed by strains of Candida spp. during episodes of persistent Candidemia, BP.PD; 20/12082-5 - Evaluation of molecular mechanisms of resistance of Candida tropicalis in blood culture samples from 3 Latin America countries, BP.TT; 18/16641-9 - Surveillance of colonization and infection of Candida auris in Venezuelan immigrants in Brazil, BP.IC; 17/19095-2 - Investigation of the virulence and immune response against Candida auris using alternative model Caenorhabditis elegans, BP.PD

Abstract

Bloodstream Infection (BSI) caused by Candida species is a public health problem worldwide, particularly in Brazil where besides exhibiting high incidence rates, this infection presents crude mortality rates ranging between 50 and 70%. Expanding our horizons of understanding of aspects related to the epidemiology and pathogenesis of these infections, including those caused by emerging pathogens, is a critical step to optimize strategies for early diagnosis, control and treatment of Candidemia. In this context, we have established a multidisciplinary and international network of investigators to study the following aspects: 1) epidemiology of BSI caused by Candida species in medical centers in Brazil and Latin America; 2) evaluation of clonal dissemination of strains of prevalent Candida species in blood cultures obtained from patients hospitalized in tertiary care hospitals in Brazil and Spain; 3) epidemiology of invasive infections caused by cryptic Candida species and development of strategies for their early identification; 4) mechanisms of virulence and pathogenicity expressed by C. albicans strains isolated along episodes of persistent Candidemia; 5) prevalence of antifungal resistance in Candida species and molecular mechanisms involved. We have available for this study clinical, epidemiological and microbiological data related to more than 2,000 episodes of Fungemia collected along previous collaborative studies involving 21 medical centers in Brazil and Latin America. The sequencing of rDNA ITS region and analysis of protein profile by MALDI-TOF MS methods will be used for identification of Candida species. The microsatellites analysis and AFLP (Amplified Fragment Length Polymorphism) assays will be used for molecular typing and characterization of clonal dissemination of Candida strains among hospitalized patients. The genomic and transcriptomic profile of C. albicans isolates obtained from blood cultures of patients with persistent Fungemia will be analyzed for further characterization of their virulence attributes. Screening of antifungal resistant strains will be performed by broth microdilution assays (CLSI), and isolates exhibiting MICs above the ECV (Epidemiologic Cutoff Value) will be investigated for the presence of ERG11, FKS1 and FKS2 mutations and expression of efflux pumps, as well as genetic instability in mutation repair genes, depending on the resistance pattern found. Finally, we hope to consolidate our collaboration network with research centers in Brazil and abroad, working together with 8 researchers from 3 different continents to clarify relevant aspects of the natural history of infections caused by different Candida species, to validate new diagnostic tools and expand our understanding of mechanisms involved in the pathogenesis of persistent episodes of Candidemia as well as molecular mechanisms of antifungal resistance. (AU)

Scientific publications

(23)

(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)

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)

BARRETO, THAYNA LOPES; ROSSATO, LUANA; DUARTE DE FREITAS, ALINE LUIZA; MEIS, JACQUES F.; LOPES, LUCIANA BIAGINI; COLOMBO, ARNALDO LOPES; ISHIDA, KELLY. Miltefosine as an alternative strategy in the treatment of the emerging fungus Candida auris. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 56, n. 2, AUG 2020. (17/19374-9, 18/13877-1, 18/03708-8, 17/15226-5, 17/02203-7, 17/19095-2)

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)

LIMA, SORAIA L.; COLOMBO, ARNALDO L.; DE ALMEIDA JUNIOR, JOAO N.. Fungal Cell Wall: Emerging Antifungals and Drug Resistance. FRONTIERS IN MICROBIOLOGY, v. 10, NOV 21 2019. (17/02203-7)

BASTOS, RAFAEL WESLEY; ROSSATO, LUANA; VALERO, CLARA; LAGROU, KATRIEN; COLOMBO, ARNALDO LOPES; GOLDMAN, GUSTAVO H.. Potential of Gallium as an Antifungal Agent. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, DEC 11 2019. (16/07870-9, 17/02203-7, 17/19095-2)

LIMA, SORAIA LOPES; FRANCISCO, ELAINE CRISTINA; DE ALMEIDA JUNIOR, JOAO NOBREGA; SANTOS, DANIEL WAGNER DE CASTRO LIMA; CARLESSE, FABIANE; QUEIROZ-TELLES, FLAVIO; MELO, ANALY SALLES DE AZEVEDO; COLOMBO, ARNALDO LOPES. Increasing Prevalence of Multidrug-ResistantCandida haemuloniiSpecies Complex among All Yeast Cultures Collected by a Reference Laboratory over the Past 11 Years. JOURNAL OF FUNGI, v. 6, n. 3, SEP 2020. (17/02203-7)

DIAZ-GARCIA, JUDITH; ARENDRUP, MAIKEN C.; CANTON, RAFAEL; GARCIA-RODRIGUEZ, JULIO; GOMEZ, ANA; GOMEZ, ELIA; ORDEN, BEATRIZ; PARISI, GABRIELLA; PEMAN, JAVIER; POSTERARO, BRUNELLA; et al. Candidemia Candida albicans clusters have higher tendency to form biofilms than singleton genotypes. Medical Mycology, v. 58, n. 7, p. 887-895, OCT 2020. (17/02203-7)

ESTEVES, PATRICIA; LOPES LIMA, SORAIA; SALLES DE AZEVEDO MELO, ANALY; MARIA BEIRAO, ELISA; NUCCI, MARCIO; COLOMBO, ARNALDO L.. (1,3)-beta-D-glucan is able to predict therapeutic failure of patients with candidemia and not only mortality. MYCOSES, v. 64, n. 3, DEC 2020. (17/02203-7)

PECANHA-PIETROBOM, PAULA M.; COLOMBO, ARNALDO LOPES. Mind the gaps: challenges in the clinical management of invasive candidiasis in critically ill patients. Current Opinion in Infectious Diseases, v. 33, n. 6, p. 441-448, DEC 2020. (17/02203-7)

NOBREGA DE ALMEIDA, JR., JOAO; BRANDAO, IGOR B.; FRANCISCO, ELAINE C.; DE ALMEIDA, SILVIO LUIS R.; DE OLIVEIRA DIAS, PATRICIA; PEREIRA, FELICIDADE M.; SANTOS FERREIRA, FABIO; DE ANDRADE, THAISSE SOUZA; DE MIRANDA COSTA, MAGDA M.; DE SOUZA JORDAO, REGIANE T.; et al. Axillary Digital Thermometers uplifted a multidrug-susceptible Candida auris outbreak among COVID-19 patients in Brazil. MYCOSES, v. 64, n. 9, p. 1062-1072, SEP 2021. (17/02203-7)

KORDALEWSKA, MILENA; CANCINO-PRADO, GESELLE; DE ALMEIDA JR, JOAO NOBREGA; BRANDAO, IGOR BRASIL; PERAL, RENATA TIGULINI DE SOUZA; COLOMBO, ARNALDO. L. L.; PERLIN, DAVID. S. S.. Novel Non-Hot Spot Modification in Fks1 of Candida auris Confers Echinocandin Resistance. Antimicrobial Agents and Chemotherapy, v. 67, n. 6, p. 4-pg., 2023-05-24. (17/02203-7)

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)

NOBREGA DE ALMEIDA, JR., JOAO; BRANDAO, IGOR B.; FRANCISCO, ELAINE C.; DE ALMEIDA, SILVIO LUIS R.; DE OLIVEIRA DIAS, PATRICIA; PEREIRA, FELICIDADE M.; SANTOS FERREIRA, FABIO; DE ANDRADE, THAISSE SOUZA; DE MIRANDA COSTA, MAGDA M.; DE SOUZA JORDAO, REGIANE T.; et al. Axillary Digital Thermometers uplifted a multidrug-susceptible Candida auris outbreak among COVID-19 patients in Brazil. MYCOSES, JUN 2021. (17/02203-7)

REMONDI SOUZA, ANA CAROLINA; FUCHS, BETH BURGWYN; ALVES, VIVIANE DE SOUZA; JAYAMANI, ELAMPARITHI; COLOMBO, ARNALDO LOPES; MYLONAKIS, ELEFTHERIOS. Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis elegans. GENES, v. 9, n. 8, AUG 2018. (17/02203-7, 12/04769-4, 13/07405-6)

ROSSATO, LUANA; COLOMBO, ARNALDO LOPES. Candida auris: What Have We Learned About Its Mechanisms of Pathogenicity?. FRONTIERS IN MICROBIOLOGY, v. 9, DEC 12 2018. (17/19095-2, 17/02203-7)

ROSENBERG, ALEXANDER; ENE, V, IULIANA; BIBI, MAAYAN; ZAKIN, SHIRI; SEGAL, ELLA SHTIFMAN; ZIV, NAOMI; DAHAN, ALON M.; COLOMBO, ARNALDO LOPES; BENNETT, RICHARD J.; BERMAN, JUDITH. Antifungal tolerance is a subpopulation effect distinct from resistance and is associated with persistent candidemia. NATURE COMMUNICATIONS, v. 9, JUN 25 2018. (17/02203-7)

GUINEA, JESUS; ARENDRUP, MAIKEN C.; CANTON, RAFAEL; CANTON, EMILIA; GARCIA-RODRIGUEZ, JULIO; GOMEZ, ANA; DE LA PEDROSA, ELIA GOMEZ G.; HARE, RASMUS K.; ORDEN, BEATRIZ; SANGUINETTI, MAURIZIO; et al. Genotyping Reveals High Clonal Diversity and Widespread Genotypes of Candida Causing Candidemia at Distant Geographical Areas. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 10, MAY 5 2020. (17/02203-7)

DIAZ-GARCIA, JUDITH; ARENDRUP, MAIKEN C.; CANTON, RAFAEL; GARCIA-RODRIGUEZ, JULIO; GARCIA DE LA PEDROSA, ELIA GOMEZ; PARISI, GABRIELLA; PEMAN, JAVIER; POSTERARO, BRUNELLA; SANGUINETTI, MAURIZIO; DA MATTA, DANIEL ARCHIMEDES; et al. Lack of relationship between genotype and virulence in Candida species. REVISTA IBEROAMERICANA DE MICOLOGIA, v. 38, n. 1, p. 9-11, JAN-MAR 2021. (17/02203-7)

DE JONG, AUKE W.; FRANCISCO, ELAINE C.; DE ALMEIDA, JR., JOAO NOBREGA; BRANDAO, IGOR B.; PEREIRA, FELICIDADE M.; DIAS, PEDRO H. PRESTA; DE MIRANDA COSTA, MAGDA M.; DE SOUZA JORDAO, REGIANE T.; VU, DUONG; COLOMBO, ARNALDO L.; et al. Nanopore Genome Sequencing and Variant Analysis of the Susceptible Candida auris Strain L1537/2020, Salvador, Brazil. Mycopathologia, v. 186, n. 6, OCT 2021. (17/02203-7)

DANESHNIA, FARNAZ; HILMIOGLU POLAT, SULEYHA; ILKIT, MACIT; SHOR, ERIKA; DE ALMEIDA, JOAO NOBREGA; FAVARELLO, LARISSA M.; COLOMBO, ARNALDO LOPES; ARASTEHFAR, AMIR; PERLIN, DAVID S.. Determinants of fluconazole resistance and the efficacy of fluconazole and milbemycin oxim combination against Candida parapsilosis clinical isolates from Brazil and Turkey. FRONTIERS IN FUNGAL BIOLOGY, v. 3, p. 9-pg., 2022-07-28. (17/02203-7)

FRANCISCO, ELAINE CRISTINA; DE JONG, AUKE WIEBREN; COLOMBO, ARNALDO LOPES. Candida haemulonii Species Complex: A Mini-review. Mycopathologia, v. N/A, p. 9-pg., 2023-06-30. (17/02203-7, 19/24960-0)

AGNELLI, CAROLINE; VALERIO, MARICELA; BOUZA, EMILIO; GUINEA, JESUS; SUKIENNIK, TERESA; GUIMARAES, THAIS; QUEIROZ-TELLES, FLAVIO; MUNOZ, PATRICIA; COLOMBO, ARNALDO LOPES. Prognostic factors of Candida spp. bloodstream infection in adults: A nine-year retrospective cohort study across tertiary hospitals in Brazil and Spain. LANCET REGIONAL HEALTH-AMERICAS, v. 6, p. 9-pg., 2022-02-01. (17/02203-7)

AGNELLI, CAROLINE; GUIMARAES, THAIS; SUKIENNIK, TERESA; LIMA, PAULO ROBERTO PASSOS; SALLES, MAURO JOSE; BREDA, GIOVANNI LUIS; QUEIROZ-TELLES, FLAVIO; MAGRI, MARCELLO MIHAILENKO CHAVES; MENDES, ANA VERENA; CAMARGO, LUIS FERNANDO ARANHA; et al. Prognostic Trends and Current Challenges in Candidemia: A Comparative Analysis of Two Multicenter Cohorts within the Past Decade. JOURNAL OF FUNGI, v. 9, n. 4, p. 11-pg., 2023-04-01. (17/02203-7)