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

Grant number: 17/02203-7
Support type:Research Projects - Thematic Grants
Duration: November 01, 2017 - October 31, 2022
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Arnaldo Lopes Colombo
Grantee:Arnaldo Lopes Colombo
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Analy Salles de Azevedo Melo ; Jacques Franciscus Meis ; João Nóbrega de Almeida Júnior ; Marcio Luiz Moore Nucci
Associated scholarship(s):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


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
(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)
ROSSATO, LUANA; COLOMBO, ARNALDO LOPES. Candida auris: What Have We Learned About Its Mechanisms of Pathogenicity?. FRONTIERS IN MICROBIOLOGY, v. 9, DEC 12 2018. Web of Science Citations: 5.
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. Web of Science Citations: 3.
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. Web of Science Citations: 17.

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