Pulmonary Aspergillosis and correlation between clinical forms and differential expression of virulence attributes in Aspergillus fumigatus

• Grant number: 14/50294-3
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2015 - April 30, 2017
• Field of knowledge: Health Sciences - Medicine
• Convênio/Acordo: University of Manchester
• Principal Investigator: Arnaldo Lopes Colombo
• Grantee: Arnaldo Lopes Colombo
• Principal researcher abroad: David Denning
• Institution abroad: University of Manchester, England
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 12/19100-2 - Evaluation of the anti-tumour and angiogenic activity of the Aspergillus fumigatus secretome, AP.R

Abstract

Aspergillus fumigatus is a human fungal pathogen able to cause invasive aspergillosis (IA) associated with high mortality rates in immunocompromised patients and chronic pulmonary aspergillosis (CPA) in immunocompetent individuais with previous pulmonary lesions. Although Brazil is an endemic country for tuberculosis, the main underlying condition associated with CPA, little is known about the epidemiology of CPA in our country. Preliminary and original data from our laboratory strongly suggests that A. fumigatus obtained from patients with different clinical forms of pulmonary aspergillosis presents distinct composition in their secretome. Our hypothesis is that differences in the pulmonary microenvironment may trigger different fungal cell signaling and expression of virulence factors. To better investigate this finding, the collaboration between UNIFESP-FAPESP and The University of Manchester will be important to generate: (i) clinical and laboratorial protocols necessary to organize the Brazilian Registry of CPA cases, a relevant step to characterize the burden of this infection in our region as well as collect clinical data and Aspergillus strains for our investigation; (ii) to establish new strategies to investigate differences in cell signaling pathways related to the expression of virulence factors by A. fumigatus, including transcriptome and metabolome analysis; (iii) to organize a multidisciplinary group of investigators form both institutions able to apply for new grants necessary to sponsor research in the pathogenesis of pulmonary aspergillosis; (iv) to divulgate knowledge on the pathogenesis, diagnosis and clinical management of pulmonary aspergillosis to health care workers, students and investigators from reference medical centers and Universities in Sao Paulo. Furthermore, we may gain crucial new insights in the pathogenesis of aspergillosis by looking at virulence atributes of A. fumigatus, openning perspectives for the development of new therapeutical strategies against this fungal infection. (AU)