PXD004398

PXD004398 is an original dataset announced via ProteomeXchange.

Title	Giardia Secretome Highlights Secreted Tenascins as a Key Component of Pathogenesis
Description	Giardia causes more episodes of illness worldwide than any other parasite. It is a flagellated cyst-forming enteric pathogen that inhabits the lumen of the small intestine and although it is clear that more and less virulent strains do occur, pathogenesis and virulence of Giardia remains poorly understood. Identification of Giardia virulence factors is highly desirable since their expression would be the best indicator for determining disease outcome. The advent of quantitative proteomics has been timely in investigating which proteins are likely to be secreted virulence factors. Here we successfully apply such analyses to the whole parasite and to the supernatants derived from the parasite, in order to ascertain a repertoire of secreted proteins. In our initial analysis we compared replicates of Giardia cells and culture supernatants from the two major lineages which cause human disease – assemblage A and assemblage B. The genome of Giardia is believed to contain open reading frames which could encode as many as 6000 proteins. In our study we confirm expression of ~1600 proteins from each assemblage, the vast majority of which being common to both lineages. To look for actual enrichment of secreted proteins, we considered the ratio of proteins in the supernatant compared with the pellet. This simple method defines a small group of enriched proteins, putatively secreted at a steady state by cultured growing Giardia trophozoites of both assemblages. This secretome contains a high proportion annotated to have N’ terminus signal peptides, with some showing evidence of having recently evolved under strong positive selective pressure. The most abundant secreted proteins include known virulence factors such as the Cathepsin B cysteine proteases and members of a Giardia superfamily of Cysteine Rich Proteins which comprises VSPs, HCMPs and a new class of virulence factors, the Giardia Tenascins. Since we also find that physiological function of human enteric epithelial cells can be disrupted by soluble factors even in the absence of the trophozoites we are able to propose a straightforward model of Giardia pathogenesis incorporating key roles for the major Giardia derived soluble mediators.
HostingRepository	PRIDE
AnnounceDate	2018-01-10
AnnouncementXML	Submission_2019-02-12_08:09:05.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD004398
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Dong Xia
SpeciesList	scientific name: Giardia sp.; NCBI TaxID: 5744;
ModificationList	HNE; Bacillosamine; GluGlu; Hex; Methylphosphonate; Delta:H(4)C(2)O(-1)S(1); Decanoyl; Propionamide; GlycerylPE; PhosphoHex; Deamidated; sulfo+amino; Trp->Oxolactone; Methylamine; DTT_ST; Myristoyl; Cation:K; Delta:S(-1)Se(1); Glycosyl; Gln->pyro-Glu; Met->Hsl; Diethylphosphate; Guanidinyl; DAET; HexNAc(2); Chlorination; Fluoro; Ammonia-loss; Nethylmaleimide+water; Ethylphosphate; ISD_z+2_ion; Oxidation; Piperidine; AEC-MAEC; Carboxy; O-pinacolylmethylphosphonate; BITC; PET; Quinone; Ethanolamine; Cation:Na; maleimide3; Sulfo; GlyGly; Deoxy; Malonyl; Methyl+Deamidated; HPG; GluGluGlu; Formyl; Carbamyl; LG-anhydrolactam; Phosphoguanosine; 3-deoxyglucosone; Thiophospho; Sulfide; NDA; Amino; Ammonium; Dimethyl; Menadione; Delta:H(5)C(2); Lipoyl; Cation:Cu[I]; Pro->Pyrrolidone; Crotonaldehyde; Met->Hse; Dethiomethyl; Cytopiloyne; Amidated; Thioacyl; Diethyl; Lys->AminoadipicAcid; Pro->pyro-Glu; Ethanolyl; Phospho; PEITC; Propargylamine; Acetyl; BisANS; Galactosyl; Cation:Ni[II]; Nitro; dichlorination; Carboxymethyl; 4-ONE+Delta:H(-2)O(-1); Hex1HexNAc1; HexNAc; Carbamidomethyl; Cation:Ca[II]; 3sulfo; Biotin-PEO-Amine; Glycerophospho; Glu->pyro-Glu; GluGluGluGlu; Carboxyethyl; Hex(1)HexNAc(1)NeuAc(1); dHex; Delta:H(2)C(2); Ethyl; Cation:Li; O-Isopropylmethylphosphonate; Cation:Fe[II]; Isopropylphospho; Methyl; LG-pyrrole; AEBS; Pyridylacetyl; Dihydroxyimidazolidine; Hex(2)HexNAc(2)dHex(1); Methylmalonylation; Phosphopropargyl; HNE-Delta:H(2)O; Delta:H(4)C(3); TNBS; Didehydro; Cytopiloyne+water; Trp->Kynurenin; Glu; Arg->GluSA; Dansyl; Iminobiotin; SMA; Iodo; BHAc; HexN; Diisopropylphosphate; thioacylPA; Nmethylmaleimide; G-H1; Lys->Allysine; Amidine; ethylamino; maleimide; O-Methylphosphate; Dehydrated; Biotin; pyrophospho; Dioxidation; Ethyl+Deamidated; Benzoyl; Carbofuran; Hex(2); glycidamide
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2016-06-21 05:51:41	ID requested
1	2018-01-10 02:36:49	announced
⏵ 2	2019-02-12 08:09:07	announced	Updated publication reference for PubMed record(s): 29385462.

Dubourg A, Xia D, Winpenny JP, Al Naimi S, Bouzid M, Sexton DW, Wastling JM, Hunter PR, Tyler KM, Giardia secretome highlights secreted tenascins as a key component of pathogenesis. Gigascience, 7(3):1-13(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Giardia, Secretome, Pathogenesis

Jonathan Wastling
contact affiliation	Faculty of Natural Sciences, Keele University, UK
contact email	j.wastling@keele.ac.uk
lab head
Dong Xia
contact affiliation	Infection Biology
contact email	d.xia@liv.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004398
     1. Label: PRIDE project
     2. Name: Giardia Secretome Highlights Secreted Tenascins as a Key Component of Pathogenesis