PXD052778-1

PXD052778 is an original dataset announced via ProteomeXchange.

Title	Haptoglobin is dispensable for haemoglobin uptake by Trypanosoma brucei
Description	Trypanosoma brucei requires haemoglobin for survival in the mammalian bloodstream. Haptoglobin (Hp), a host protein known to bind haemoglobin, was determined as a key component for haemoglobin acquisition by the parasite. Here, we investigated the impact of haptoglobin deficiency on T. brucei brucei infection and the parasite´s capacity to internalise haemoglobin in the Hp-/- mouse model. The infected Hp-/- mice exhibited normal disease progression, with minimal weight loss and no apparent organ pathology similarly to control mice. While the proteomic profile of mouse sera significantly changed in response to T. b. brucei, no differences in the infection response markers of blood plasma have been observed between Hp-/- and control Black mice. Similarly, very few quantitative differences have been observed between the proteomes of parasites harvested from Hp-/- and Black mice, entailing both endogenous proteins and internalised host proteins. While haptoglobin was indeed absent from parasites isolated from Hp-/-mice, haemoglobin peptides were unexpectedly detected in parasites from both Hp-/- and Black mice. This was verified by western blotting, EM immunolabeling of parasites cryosections, and analytical quantification of haem cofactors in the parasites extracts. Combined, the data support the Hp dispensability for haemoglobin internalisation by T. b. brucei during infection in mice. To further explore this phenomenon, we have generated T. b. brucei haptoglobin-haemoglobin receptor (HpHbR) knock-outs and used them to infect Hp-/- and control mice. The HpHbR-knock-out trypanosomes internalised significantly less haemoglobin from Hp-/- mice compared to those isolated from Black mice strongly suggesting that T. b. brucei employs an HpHbR-independent Hp-mediated mode for haemoglobin internalisation. Our study reveals a so-far hidden flexibility of haemoglobin acquisition by T. b. brucei and offers novel insights into alternative haemoglobin uptake pathways.
HostingRepository	PRIDE
AnnounceDate	2024-07-16
AnnouncementXML	Submission_2024-07-16_14:56:52.809.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marek Vrbacky
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Trypanosoma brucei brucei TREU927; NCBI TaxID: 185431;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-02 14:56:12	ID requested
⏵ 1	2024-07-16 14:56:53	announced

10.3389/FIMMU.2024.1441131;

submitter keyword: blood parasite, hemoglobin, haptoglobin,Trypanosoma brucei brucei, haptoglobin knock-out mouse

Jan Perner
contact affiliation	Institute of Parasitology, Biology Centre, Czech Academy of Sciences Ceske Budejovice (Budweis) Czech Republic
contact email	perner@paru.cas.cz
lab head
Marek Vrbacky
contact affiliation	Czech Academy of Sciences
contact email	proteom.krc@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD052778
     1. Label: PRIDE project
     2. Name: Haptoglobin is dispensable for haemoglobin uptake by Trypanosoma brucei