PXD002731

PXD002731 is an original dataset announced via ProteomeXchange.

Title	Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A
Description	Background: The pathogenic yeast Cryptococcus neoformans causes life-threatening meningoencephalitis in individuals suffering from HIV/AIDS. The cyclic-AMP/protein kinase A (PKA) signal transduction pathway regulates the production of extracellular virulence factors in C. neoformans, but the influence of the pathway on the secretome has not been investigated. In this study, we performed quantitative proteomics using galactose-inducible and glucose-repressible expression of the PKA1 gene encoding the catalytic subunit of PKA to identify regulated proteins in the secretome. Results: We identified 61 secreted proteins and found that changes in PKA1 expression influenced the extracellular abundance of five proteins, including the Cig1 and Aph1 proteins with known roles in virulence. We also observed a change in the secretome profile upon induction of Pka1 from proteins primarily involved in catabolic and metabolic processes to an expanded set that included proteins for translational regulation and the response to stress. We further characterized the secretome data using enrichment analysis and by predicting conventional versus non-conventional secretion. Targeted proteomics of the Pka1-regulated proteins allowed us to identify the secreted proteins in lysates of phagocytic cells containing C. neoformans, and in samples from infected mice. This analysis also revealed that modulation of PKA1 expression influences the intracellular survival of cryptococcal cells upon phagocytosis. Conclusions: Overall, we found that the cAMP/PKA pathway regulates specific components of the secretome including proteins that affect the virulence of C. neoformans. The detection of secreted cryptococcal proteins from infected phagocytic cells and tissue samples suggests their potential utility as biomarkers of infection.
HostingRepository	PRIDE
AnnounceDate	2015-10-13
AnnouncementXML	Submission_2015-10-13_01:02:29.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Geddes-McAlister
SpeciesList	scientific name: Cryptococcus neoformans var. grubii H99W; NCBI TaxID: 1432138;
ModificationList	monohydroxylated residue; carbamoylated residue; dimethylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-17 00:13:08	ID requested
⏵ 1	2015-10-13 01:02:31	announced

Geddes JM, Croll D, Caza M, Stoynov N, Foster LJ, Kronstad JW, Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A. BMC Microbiol, 15():206(2015) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: Quantitative proteomics

fungal pathogenesis

secretome

PKA

virulence factors

biomarkers

multiple reaction monitoring

Jim Kronstad
contact affiliation	Michael Smith Laboratories, University of British Columbia
contact email	kronstad@msl.ubc.ca
lab head
Jennifer Geddes-McAlister
contact affiliation	Max Planck Institute for Biochemistry
contact email	geddes@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002731
     1. Label: PRIDE project
     2. Name: Secretome profiling of Cryptococcus neoformans reveals regulation of a subset of virulence-associated proteins and potential biomarkers by protein kinase A