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Hematogenic candidiasis: a multidisciplinary approach for the improvement of diagnostic tools and caracterization of biomarkers related to its prognosis

Grant number: 07/08575-1
Support type:Research Projects - Thematic Grants
Duration: June 01, 2008 - November 30, 2012
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
Co-Principal Investigators:Marcelo Ribeiro da Silva Briones
Assoc. researchers:Analy Salles de Azevedo Melo ; Guilherme Maranhão Chaves
Associated scholarship(s):10/17179-5 - Proteomics as a strategy to identify biomarkers for early diagnosis of candidemia, BP.PD
10/02752-1 - Identification of species from the Candida "para-meta-ortho-psilosis" complex using real-time PCR, BP.MS
09/10155-6 - Development and clinical validation of molecular methods for early diagnosis of invasive candidiasis and aspergillosis, BP.PD
09/01230-4 - Clinical aplications on the molecular systematic of Candida spp. in the perspective of comparative genomics of gene genealogies and Bayesian analyses, BP.PD

Abstract

Haematogenic infections caused by Candida albicans in hospitalized patients are of great impact in worldwide public health in terms of morbidity and mortality. Recent progress on the development of antifungal drugs has not reduced the lethality of candidaemia which is still approximately 40 to 50% of infected patients. The objectives of this project are therefore (1) to improve diagnostic tools for haematogenic candidiasis using large scale analysis of rDNA internal transcribed spacer (ITS) as a rapid and accurate identification method for emerging species of Candida spp, (2) to develop molecular typing methods using mitocondrial DNA hypervariable regions for the identication of Candida spp outbreaks, (3) to contribute the understanding of host- pathogen interactions during the onset of haemopathogenic infection by C. albicans and (4) to characterize mutations in "Toll like" receptors (TLRs) and other pattern recognition receptors (PRRs) that recognize fungal glucans in patients with different clinical manifestations. To address objective (1) we will sequence intergenic spacers (IGS) and ITS of rDNA of C. albicans, C. dubliniensis, C. glabrata, C. parapsilosis, C. orthopsilosis, C. metapsilosis, etc. These sequences will be compared with other database sequences for identification. These results will be used to establish a gold standard method for rapid species identification of clinical isolates. The identification using molecular methods is mandatory to resolve inconsistencies arising from conventional methods in the identification of emerging yeasts such as C. dubliniensis, C. orthopsilosis and C. metapsilosis. For objective (2) we propose to use comparative genomics of mitocondrial DNA for typing and for objective (3) we plan to characterize virulence factors in fungal samples isolated from patients with different clinical outcomes. We are going to analyse the following virulence factors: adhesion to epithelial cells, morphogenesis, aspartyl proteinases (Saps) and phospholipase secretion and interaction with neutrophils. For objective (4) we plan to study the correlation of human PRRs, genetic diversity and host susceptibility to Candida spp. infection. The haplotypes of PRRs such as dectin 1 and Toll like receptor 2 will be sequenced from phagocitic cells obtained from blood samples of candidaemic patients routinely assisted by our group of clinicians encharged of blood stream infections patients care. (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)
IRINYI, LASZLO; SERENA, CAROLINA; GARCIA-HERMOSO, DEA; ARABATZIS, MICHAEL; DESNOS-OLLIVIER, MARIE; VU, DUONG; CARDINALI, GIANLUIGI; ARTHUR, IAN; NORMAND, ANNE-CECILE; GIRALDO, ALEJANDRA; CASSIA DA CUNHA, KEITH; SANDOVAL-DENIS, MARCELO; HENDRICKX, MARIJKE; NISHIKAKU, ANGELA SATIE; DE AZEVEDO MELO, ANALY SALLES; MERSEGUEL, KARINA BELLINGHAUSEN; KHAN, AZIZA; PARENTE ROCHA, JULIANA ALVES; SAMPAIO, PAULA; DA SILVA BRIONES, MARCELO RIBEIRO; CARMONA E FERREIRA, RENATA; DE MEDEIROS MUNIZ, MAURO; CASTANON-OLIVARES, LAURA ROSIO; ESTRADA-BARCENAS, DANIEL; CASSAGNE, CAROLE; MARY, CHARLES; DUAN, SHU YAO; KONG, FANRONG; SUN, ANNIE YING; ZENG, XIANYU; ZHAO, ZUOTAO; GANTOIS, NAUSICAA; BOTTEREL, FRANCOISE; ROBBERTSE, BARBARA; SCHOCH, CONRAD; GAMS, WALTER; ELLIS, DAVID; HALLIDAY, CATRIONA; CHEN, SHARON; SORRELL, TANIA C.; PIARROUX, RENAUD; COLOMBO, ARNALDO L.; PAIS, CELIA; DE HOOG, SYBREN; ZANCOPE-OLIVEIRA, ROSELY MARIA; TAYLOR, MARIA LUCIA; TORIELLO, CONCHITA; DE ALMEIDA SOARES, CELIA MARIA; DELHAES, LAURENCE; STUBBE, DIRK; DROMER, FRANCOISE; RANQUE, STEPHANE; GUARRO, JOSEP; CANO-LIRA, JOSE F.; ROBERT, VINCENT; VELEGRAKI, ARISTEA; MEYER, WIELAND. International Society of Human and Animal Mycology (ISHAM)-ITS reference DNA barcoding database-the quality controlled standard tool for routine identification of human and animal pathogenic fungi. Medical Mycology, v. 53, n. 4, p. 313-337, MAY 2015. Web of Science Citations: 93.
DE AZEVEDO BASTOS, VIVIANE REIS; DE CASTRO LIMA SANTOS, DANIEL WAGNER; BARBOSA PADOVAN, ANA CAROLINA; AZEVEDO MELO, ANALY SALLES; MAZZOLIN, MILENE DE ABREU; ARANHA CAMARGO, LUIS FERNANDO; COLOMBO, ARNALDO LOPES. Early Invasive Pulmonary Aspergillosis in a Kidney Transplant Recipient Caused by Aspergillus lentulus: First Brazilian Report. Mycopathologia, v. 179, n. 3-4, p. 299-305, APR 2015. Web of Science Citations: 8.
MERSEGUEL, KARINA BELLINGHAUSEN; NISHIKAKU, ANGELA SATIE; RODRIGUES, ANDERSON MESSIAS; PADOVAN, ANA CAROLINA; CARMONA E FERREIRA, RENATA; DE AZEVEDO MELO, ANALY SALLES; DA SILVA BRIONES, MARCELO RIBEIRO; COLOMBO, ARNALDO LOPES. Genetic diversity of medically important and emerging Candida species causing invasive infection. BMC INFECTIOUS DISEASES, v. 15, FEB 13 2015. Web of Science Citations: 31.
ITURRIETA-GONZALEZ, ISABEL ANTONIETA; BARBOSA PADOVAN, ANA CAROLINA; BIZERRA, FERNANDO CESAR; HAHN, ROSANE CHRISTINE; COLOMBO, ARNALDO LOPES. Multiple Species of Trichosporon Produce Biofilms Highly Resistant to Triazoles and Amphotericin B. PLoS One, v. 9, n. 10 OCT 31 2014. Web of Science Citations: 26.
BIZERRA, FERNANDO CESAR; JIMENEZ-ORTIGOSA, CRISTINA; SOUZA, ANA CAROLINA R.; BREDA, GIOVANNI LUIS; QUEIROZ-TELLES, FLAVIO; PERLIN, DAVID S.; COLOMBO, ARNALDO L. Breakthrough Candidemia Due to Multidrug-Resistant Candida glabrata during Prophylaxis with a Low Dose of Micafungin. Antimicrobial Agents and Chemotherapy, v. 58, n. 4, p. 2438-2440, APR 2014. Web of Science Citations: 33.
BARBOSA PADOVAN, ANA CAROLINA; DE AZEVEDO MELO, ANALY SALLES; COLOMBO, ARNALDO LOPES. Systematic review and new insights into the molecular characterization of the Candida rugosa species complex. Fungal Genetics and Biology, v. 61, p. 33-41, DEC 2013. Web of Science Citations: 13.
CHAVES, GUILHERME M.; TERCARIOLI, GISELA R.; PADOVAN, ANA CAROLINA B.; ROSAS, ROBERT C.; FERREIRA, RENATA C.; MELO, ANALY S. A.; COLOMBO, ARNALDO L. Candida mesorugosa sp nov., a novel yeast species similar to Candida rugosa, isolated from a tertiary hospital in Brazil. Medical Mycology, v. 51, n. 3, p. 231-242, APR 2013. Web of Science Citations: 14.
NUNES, JORGE MENESES; BIZERRA, FERNANDO CESAR; CARMONA E FERREIRA, RENATA; COLOMBO, ARNALDO LOPES. Molecular Identification, Antifungal Susceptibility Profile, and Biofilm Formation of Clinical and Environmental Rhodotorula Species Isolates. Antimicrobial Agents and Chemotherapy, v. 57, n. 1, p. 382-389, JAN 2013. Web of Science Citations: 35.
SOUZA, ANA CAROLINA R.; FERREIRA, RENATA C.; GONCALVES, SARAH S.; QUINDOS, GUILLERMO; ERASO, ELENA; BIZERRA, FERNANDO C.; BRIONES, MARCELO R. S.; COLOMBO, ARNALDO L. Accurate Identification of Candida parapsilosis (Sensu Lato) by Use of Mitochondrial DNA and Real-Time PCR. Journal of Clinical Microbiology, v. 50, n. 7, p. 2310-2314, JUL 2012. Web of Science Citations: 19.
COLOMBO, ARNALDO L.; PADOVAN, ANA CAROLINA B.; CHAVES, GUILHERME M. Current Knowledge of Trichosporon spp. and Trichosporonosis. CLINICAL MICROBIOLOGY REVIEWS, v. 24, n. 4, p. 682+, OCT 2011. Web of Science Citations: 159.

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