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Title: SEC14 is a specific requirement for secretion of phospholipase B1 and pathogenicity of Cryptococcus neoformans
Authors: Methee Chayakulkeeree
Simon Andrew Johnston
Johanes Bijosono Oei
Sophie Lev
Peter Richard Williamson
Christabel Frewen Wilson
Xiaoming Zuo
Ana Lusia Leal
Marilene Henning Vainstein
Wieland Meyer
Tania Christine Sorrell
Robin Charles May
Julianne Teresa Djordjevic
University of Sydney Faculty of Medicine
Mahidol University
University of Birmingham
National Institute of Allergy and Infectious Diseases
Universidade Federal do Rio Grande do Sul
Keywords: Biochemistry, Genetics and Molecular Biology;Immunology and Microbiology
Issue Date: 1-May-2011
Citation: Molecular Microbiology. Vol.80, No.4 (2011), 1088-1101
Abstract: Secreted phospholipase B1 (CnPlb1) is essential for dissemination of Cryptococcus neoformans to the central nervous system (CNS) yet essential components of its secretion machinery remain to be elucidated. Using gene deletion analysis we demonstrate that CnPlb1 secretion is dependent on the CnSEC14 product, CnSec14-1p. CnSec14-1p is a homologue of the phosphatidylinositol transfer protein ScSec14p, which is essential for secretion and viability in Saccharomyces cerevisiae. In contrast to CnPlb1, neither laccase 1-induced melanization within the cell wall nor capsule induction were negatively impacted in CnSEC14-1 deletion mutants (CnΔsec14-1 and CnΔsec14-1CnΔsfh5). Similar to the CnPLB1 deletion mutant (CnΔplb1), CnΔsec14-1 was hypovirulent in mice and did not disseminate to the CNS by day 14 post infection. Furthermore, macrophage expulsion of live CnΔsec14-1 and CnΔplb1 (vomocytosis) was reduced. Individual deletion of CnSEC14-2, a closely related CnSEC14-1 homologue, and CnSFH5, a distantly related SEC fourteen like homologue, did not abrogate CnPlb1 secretion or virulence. However, reconstitution of CnΔsec14-1 with CnSEC14-1 or CnSEC14-2 restored both phenotypes, consistent with functional genetic redundancy. We conclude that CnPlb1 secretion is SEC14-dependent and that C. neoformans preferentially exports virulence determinants to the cell periphery via distinct pathways. We also demonstrate that CnPlb1 secretion is essential for vomocytosis. © Published 2011 This article is a US Government work and is in the public domain in the USA.
ISSN: 13652958
Appears in Collections:Scopus 2011-2015

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