A synthetic peptide selectively kills only virulent Paracoccidioides brasiliensis yeasts

A synthetic peptide selectively kills only virulent Paracoccidioides brasiliensis yeasts

Author Kioshima, Érika Seki Autor UNIFESP Google Scholar
Aliperti, Fabiana Autor UNIFESP Google Scholar
Maricato, Juliana Terzi Autor UNIFESP Google Scholar
Mortara, Renato Arruda Autor UNIFESP Google Scholar
Bagagli, Eduardo Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Lopes, Jose Daniel Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Univ Estadual Paulista
Abstract 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.
Keywords P. brasiliensis
Virulence
Biomarkers
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 04/04471-9
Date 2011-03-01
Published in Microbes and Infection. Amsterdam: Elsevier B.V., v. 13, n. 3, p. 251-260, 2011.
ISSN 1286-4579 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 251-260
Origin http://dx.doi.org/10.1016/j.micinf.2010.10.019
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000287615000006
URI http://repositorio.unifesp.br/handle/11600/33484

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