Candida albicans-host interaction, the many faces of candida Pra1
The Candida-host interaction represents a very complex and key factor for the pathogenesis of different types of candidiasis. Candida albicans is an opportunistic human pathogen that can cause superficial, as well as life-threatening infections in immunocompromised patients. To initiating an infection, C. albicans has to evade and cross all the immune and tissue barriers. The aim of the work is to identify which protein from C. albicans contributes to these infection progresses and characterize it on a molecular level. In this project, we identified Pra1 from C. albicans as a multifunctional virulence factor which mediates C. albicans for immune and tissue evasion. Pra1 is a surface protein and also secreted into the culture medium. Different localization specializes Pra1 different functions at various sites.
(i) as a surface protein, Pra1 binds human complement regulators Factor H, FHL-1, C4BP as well as plasminogen. The attached human regulators modulate complement evasion and degradation of extra cellular matrixes, and consequently favor C. albicas invasion.
(ii) as a secreted protein, Pra1 complexes C3 in solution, blocks C3 cleavage by C3 convertases, thereby inhibits further complement amplification and progression, which leads to the blockade of the inflammatory anaphylatoxins C3a and C5a generation, C3b surface opsonization, as well as C3b mediated adhesion and uptake of the yeast by human macrophages.
(iii) Pra1 also binds to the surface of human cells. When binding to human endothelial cells, surface Pra1 functions as an invasin and mediates C. albicans for adhesion and invasion, thereby likely allows this fungal pathogen to cross the tissue layers and causes invasive disease. A detailed understanding of these multiple roles of Pra1 allow to define new strategies to interfere with and fight against Candida infection.
Publications
(2017) Kallikrein Cleaves C3 and Activates Complement. J Innate Immun , Details PubMed
(2015) Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates. PLoS One 10(2), e0113192. Details PubMed
(2013) Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans. Mol Immunol 56(3), 161-169. Details PubMed
(2011) Immune escape of the human facultative pathogenic yeast Candida albicans: the many faces of the Candida Pra1 protein. Int J Med Microbiol 301(5), 423-430. Details PubMed
(2010) Complement regulator Factor H mediates a two-step uptake of Streptococcus pneumoniae by human cells. J Biol Chem 285(30), 23486-23495. Details PubMed
Supervisor
Start of PhD
October 1, 2007
Doctoral Disputation
July 1, 2010
