Chitosan biosynthesis and virulence in the human fungal pathogen Cryptococcus gattii
Woei C. Lam,Rajendra Upadhya,Charles A. Specht,Abigail E. Ragsdale,Camaron R. Hole,Stuart M. Levitz,Jennifer K. Lodge +6 more
TLDR
The C. gattii R265 strain has evolved alternate regulation of chitosan biosynthesis under both laboratory growth conditions and during mammalian infection compared to that of C. neoformans, which is an important fungal pathogen of concern due to its ability to cause infections in individuals with no apparent immune dysfunction and an increasing geographical distribution.Abstract:
Cryptococcus gattii R265 is a hyper-virulent fungal strain responsible for the major outbreak of cryptococcosis in Vancouver Island of British Columbia in 1999. It differs significantly from C. neoformans in its natural environment, its preferred site in the mammalian host, and in the nature and mode of pathogenesis. Our previous studies in C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the present investigation reveal that the cell wall of C. gattii R265 contains 2-3-fold higher amount of chitosan compared to that of C. neoformans. The genes responsible for the biosynthesis of chitosan are highly conserved in the R265 genome; the roles of the three chitin deacetylases (CDA) have however, been modified. To deduce their roles, single, double and a triple CDA deletion strains were constructed in a R265 background and were subjected to mammalian infection studies. Unlike C. neoformans where Cda1 has a discernible role in fungal pathogenesis, in R265 Cda3 is critical for virulence. Deletion of either CDA3 alone (cda3Δ) or in combination with either CDA1 (cda1Δ3Δ) or CDA2 (cda2Δ3Δ) or both (cda1Δ2Δ3Δ) rendered the yeast cells avirulent and were cleared from the infected host. Moreover, the cda1Δ2Δ3Δ strain of R265 induced a protective response to a subsequent infection with R265. These studies shed more light into the regulation of chitosan biosynthesis of C. gattii and its subsequent effect on fungal virulence.read more
Citations
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Architecture of the dynamic fungal cell wall
Neil A. R. Gow,Megan D. Lenardon +1 more
TL;DR: The spatial organization and dynamic regulation of the wall in response to prevailing growth conditions enable fungi to thrive within changing, diverse and often hostile environments.
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Application of an optimized annotation pipeline to the Cryptococcus deuterogattii genome reveals dynamic primary metabolic gene clusters and genomic impact of RNAi loss
Patrícia Aline Gröhs Ferrareze,Corinne Maufrais,Rodrigo Silva Araujo Streit,Shelby J. Priest,Christina A. Cuomo,Joseph Heitman,Charley Christian Staats,Guilhem Janbon +7 more
TL;DR: The data suggest that there is active exchange between subtelomeric regions, and that other chromosomal regions might participate in adaptive diversification of Cryptococcus metabolite assimilation potential.
Journal ArticleDOI
Cryptococcus: History, Epidemiology and Immune Evasion
Israel Diniz-Lima,Leonardo Marques da Fonseca,Elias Barbosa da Silva-Junior,Joyce Cristina Guimarães-de-Oliveira,Leonardo Freire-de-Lima,Danielle Oliveira Nascimento,Alexandre Morrot,José O. Previato,Lucia Mendonça-Previato,Debora Decote-Ricardo,Celio Geraldo Freire-de-Lima +10 more
TL;DR: It is important to point out that not only C. gattii, but the Cryptococcus species complex produces a polysaccharidic capsule with immunomodulatory properties, enabling the pathogenic species of Cryptococccus to subvert the host immune response during the establishment of cryptococcosis, facilitating its dissemination in the infected organism.
Journal ArticleDOI
Chitin deacetylase: from molecular structure to practical applications
Ziyang Huang,Xueqin Lv,Guoyun Sun,Xinzhu Mao,Wei Liu,Yanfeng Liu,Jianghua Li,Guocheng Du,Long Liu +8 more
TL;DR: Wang et al. as discussed by the authors summarized the latest knowledge of CDAs, especially for heterologous expression systems and directed evolution strategies, which may contribute to the industrial production and future application of chitin deacetylases.
Journal ArticleDOI
Cell wall composition in Cryptococcus neoformans is media dependent and alters host response, inducing protective immunity
TL;DR: In this article , the role of growth conditions on the cryptococcal cell wall and virulence of C. neoformans has been investigated in the context of yeast nitrogen base (YNB) and peptone and dextrose (YPD) media.
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