Fabiana Aliperti, Eduardo Bagagli, Erika Seki Kioshima, Juliana Terzi Maricato, José Daniel Lopes, Mario Mariano, Renato A. Mortara, Universidade Federal de São Paulo (UNIFESP), Universidade de São Paulo (USP), Univ Estadual Paulista, and Universidade Estadual Paulista (Unesp)
Made available in DSpace on 2013-09-27T14:54:31Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2013-09-27T14:54:31Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2013-09-27T14:54:31Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2013-09-30T18:38:38Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2013-09-30T18:38:38Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:51:13Z No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Made available in DSpace on 2013-09-30T18:38:38Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:51:13Z No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Made available in DSpace on 2014-05-20T13:51:13Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2014-05-20T13:51:13Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2013-09-30T18:38:38Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:51:13Z No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:51:13Z No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Made available in DSpace on 2014-05-20T13:51:13Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Made available in DSpace on 2014-05-20T13:51:13Z (GMT). No. of bitstreams: 1 WOS000287615000006.pdf: 903468 bytes, checksum: 40a6017ece6a8fab966c54d4ea5be9e3 (MD5) Previous issue date: 2011-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This work was conducted to identify virulence biomarkers for Paracoccidioides brasiliensis (Pb), the fungus responsible for Paracoccidioidomycosis (PCM), a systemic disease endemic in Latin America. Measurement of mortality showed that all B10.A mice were killed after 250 days by the virulent Pb18 isolate while only one of the mice that received the attenuated counterpart died. Also, number of lung CFUs from virulent Pb18 inoculated mice were much higher when these isolates were compared. Phage display methodology allowed selection of three phages that specifically bound to virulent Pb18. Variability of p04 phage binding to different Pb isolates were examples of variability of expression by the fungus of its binding molecule, strongly suggesting p04 as a biomarker of virulence. In vitro, its derived peptide pep04 killed only virulent fungi, and confocal microscopy showed that it was internalized only by the virulent isolate. Pep04 blocked establishment of Pb infection in mice and virulent Pb18 pre-incubated with p04 showed significantly inhibited lung infection. Furthermore, infected mice treated with p04 showed highly significant reduction in lung CFUs. These findings firmly establish p04 as a biomarker of Pb virulence. Therefore, after proper peptide engineering, p04 may become a useful adjuvant for the distressing treatment of PCM. (C) 2010 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. Univ Fed São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, Brazil State Univ São Paulo, Dept Microbiol, Inst Biosci Botucatu, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Hlth, São Paulo, Brazil State Univ São Paulo, Dept Microbiol, Inst Biosci Botucatu, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Hlth, São Paulo, Brazil FAPESP: 04/04471-9