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The endosomal sorting complex required for transport machinery influences haem uptake and capsule elaboration in C ryptococcus neoformans
Author(s) -
Hu Guanggan,
Caza Mélissa,
Cadieux Brigitte,
Bakkeren Erik,
Do Eunsoo,
Jung Won Hee,
Kronstad James W.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12985
Subject(s) - escrt , biology , endosome , virulence , mutant , microbiology and biotechnology , transport protein , cryptococcus neoformans , tsg101 , biochemistry , gene , microrna , microvesicles , intracellular
Summary Iron availability is a key determinant of virulence in the pathogenic fungus C ryptococcus neoformans . Previous work revealed that the ESCRT (endosomal sorting complex required for transport) protein Vps23 functions in iron acquisition, capsule formation and virulence. Here, we further characterized the ESCRT machinery to demonstrate that defects in the ESCRT‐II and III complexes caused reduced capsule attachment, impaired growth on haem and resistance to non‐iron metalloprotoporphyrins. The ESCRT mutants shared several phenotypes with a mutant lacking the pH‐response regulator R im101, and in other fungi, the ESCRT machinery is known to activate R im101 via proteolytic cleavage. We therefore expressed a truncated and activated version of R im101 in the ESCRT mutants and found that this allele restored capsule formation but not growth on haem, thus suggesting a R im101‐independent contribution to haem uptake. We also demonstrated that the ESCRT machinery acts downstream of the c AMP /protein kinase A pathway to influence capsule elaboration. Defects in the ESCRT components also attenuated virulence in macrophage survival assays and a mouse model of cryptococcosis to a greater extent than reported for loss of R im101. Overall, these results indicate that the ESCRT complexes function in capsule elaboration, haem uptake and virulence via R im101‐dependent and independent mechanisms.