Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Infected erythrocytes and plasma proteomics reveals a specific protein signature of severe malaria

ABSTRACT: Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), remains fatal for 15 to 25% of affected children despite the availability of treatment. P. falciparum infects and multiplies in erythrocytes, contributing to anemia, parasite sequestration, and inflammation. An unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to study the complex mechanisms underlying CM. A significant down-regulation of proteins from the ubiquitin-proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) were associated with infected erythrocytes from CM patients. At the plasma level, the samples clustered according to clinical presentation. Significantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger cohort (n=340). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroblasts and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers.

SUBMITTER: Jérémy Fraering

PROVIDER: S-SCDT-10_1038-S44321-023-00010-0 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Infected erythrocytes and plasma proteomics reveal a specific protein signature of severe malaria.

Project description:Severe malaria (SM) is a life-threatening condition caused by Plasmodium falciparum and the most severe presentation is cerebral malaria (CM) mostly affecting children under five years old. The comprehensive understanding of the complex mechanisms driving the pathophysiology of CM, which encompasses both host and parasite factors, remains insufficiently elucidated. This study analyzed clinical isolates from Beninese children using liquid chromatography-mass spectrometry to identify differentially expressed proteins in SM compared to uncomplicated malaria (UM) patients. We showed a down-regulation of proteins involved in ubiquitination and proteasomal protein degradation in infected erythrocytes from CM patients. In plasma we observed that proteasome 20S components were more abundant in SM patients, which could potentially be useful as a severity biomarker. Furthermore, transferrin receptor protein 1 was specifically upregulated in CM infected erythrocyte isolates which raises the hypothesis that parasites causing CM could preferably infect reticulocytes or erythroid precursors. Consistently with this hypothesis we also found that parasite proteins implicated in distinct biosynthesis pathways were upregulated in CM. Moreover, functional analysis showed deregulated iron metabolism and ferroptosis pathways associated with CM presentation. Further investigations are required to confirm these findings and determine their potential for clinical application.

2024-02-01 | PXD042503 | Pride

Infected erythrocytes and plasma proteomics reveal a specific protein signature of severe malaria

Project description:Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), claims the life of 15 to 25% of admitted children despite treatment. P. falciparum infects and multiplies in human erythrocytes, contributing to anemia, parasite sequestration, and inflammation in the host. In this study, an unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to decipher the complex mechanisms underlying the pathophysiology of CM and the corresponding host-parasite interactions. A significant down-regulation of proteins from the ubiquitin-proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) was associated with infected erythrocytes from CM patients. Further functional analysis showed dysregulated iron metabolism and ferroptosis pathways associated with CM. At the plasma level, the samples clustered according to clinical presentation. Importantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger confirmation cohort (n=274). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroid precursors and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers.

2024-02-01 | PXD043033 | Pride

Quantitative proteomics reveals specific protein regulation of severe hypospadias.

Project description:BackgroundThe etiological mechanism of hypospadias is multifactorial and may be heterogeneous by severity. To date, very limited analyses on proteome in hypospadias have been conducted, and there are still no severe hypospadias proteomics analyses.MethodsIn our study, tandem mass tag (TMT)-based quantitative proteomics was performed, exploring the clinical samples from hypospadias patients and healthy donators, in order to identify distinctly expressed proteins for severe hypospadias. To further uncover the mechanistic links in these complex proteomics data, we performed several core ingenuity pathway analyses (IPA) to predict, based on these observed different expression of proteins (DEPs).ResultsCompared with the unaffected controls, 299 proteins were found to be down-regulated and 176 proteins up-regulated in severe hypospadias foreskin tissues. Functional annotation revealed that these DEPs were mainly in the extracellular space and were associated with complement activation and coagulation cascades. Similarly, the IPA core analysis revealed enriched pathways of the acute phase response signaling and complement system, demonstrating that by mediating their targeted, differentiated expressed proteins (A2M, APOE, C4A/C4B, C5, CAT, CD74, CFP, CREB1, CTSB, FGA, FGB, FGG, FN1, FOS, HP, LYZ, PF4, RBP1, S100A12, SERPINA3, SLC2A1, and THBS1) may be involved in the activation of myeloid cell degranulation, phagocytes degranulation, molecule secretion, and were mainly regulated by CSF1, JNK, STAT1, and STAT3.ConclusionsOur findings raise questions regarding the role of inflammatory activity in the pathology of severe hypospadias. This approach highlights the possibility of the use of non-surgical approaches to limit fibrotic signals and function, which is a promising potential therapeutic strategy for hypospadias patients.

| S-EPMC9085921 | biostudies-literature

Plasma proteomics reveals markers of metabolic stress in HIV infected children with severe acute malnutrition.

Project description:HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.

| S-EPMC7343797 | biostudies-literature

Protein Modification Characteristics of the Malaria Parasite Plasmodium falciparum and the Infected Erythrocytes.

Project description:Malaria elimination is still pending on the development of novel tools that rely on a deep understanding of parasite biology. Proteins of all living cells undergo myriad posttranslational modifications (PTMs) that are critical to multifarious life processes. An extensive proteome-wide dissection revealed a fine PTM map of most proteins in both Plasmodium falciparum, the causative agent of severe malaria, and the infected red blood cells. More than two-thirds of proteins of the parasite and its host cell underwent extensive and dynamic modification throughout the erythrocytic developmental stage. PTMs critically modulate the virulence factors involved in the host-parasite interaction and pathogenesis. Furthermore, P. falciparum stabilized the supporting proteins of erythrocyte origin by selective demodification. Collectively, our multiple omic analyses, apart from having furthered a deep understanding of the systems biology of P. falciparum and malaria pathogenesis, provide a valuable resource for mining new antimalarial targets.

| S-EPMC7857547 | biostudies-literature

Electrophysiological studies of malaria parasite-infected erythrocytes: current status.

Project description:The altered permeability characteristics of erythrocytes infected with malaria parasites have been a source of interest for over 30 years. Recent electrophysiological studies have provided strong evidence that these changes reflect transmembrane transport through ion channels in the host erythrocyte plasma membrane. However, conflicting results and differing interpretations of the data have led to confusion in this field. In an effort to unravel these issues, the groups involved recently came together for a week of discussion and experimentation. In this article, the various models for altered transport are reviewed, together with the areas of consensus in the field and those that require a better understanding.

| S-EPMC2746352 | biostudies-literature

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria.

Project description:Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria.

| S-EPMC3990714 | biostudies-literature

Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity.

Project description:Plasmodium falciparum is the major cause of malaria globally and is transmitted by mosquitoes. During parasitic development, P. falciparum-infected erythrocytes (P. falciparum-IEs) express multiple polymorphic proteins known as variant surface antigens (VSAs), including the P. falciparum erythrocyte membrane protein 1 (PfEMP1). VSA-specific antibodies are associated with protection from symptomatic and severe malaria. However, the importance of the different VSA targets of immunity to malaria remains unclear, which has impeded an understanding of malaria immunity and vaccine development. In this study, we developed assays using transgenic P. falciparum with modified PfEMP1 expression to quantify serum antibodies to VSAs among individuals exposed to malaria. We found that the majority of the human antibody response to the IE targets PfEMP1. Furthermore, our longitudinal studies showed that individuals with PfEMP1-specific antibodies had a significantly reduced risk of developing symptomatic malaria, whereas antibodies to other surface antigens were not associated with protective immunity. Using assays that measure antibody-mediated phagocytosis of IEs, an important mechanism in parasite clearance, we identified PfEMP1 as the major target of these functional antibodies. Taken together, these data demonstrate that PfEMP1 is a key target of humoral immunity. These findings advance our understanding of the targets and mediators of human immunity to malaria and have major implications for malaria vaccine development.

| S-EPMC3428085 | biostudies-literature

Proteomic analysis reveals pathogen-derived biomarkers of acute babesiosis in erythrocytes, plasma, and urine of infected hamsters.

Project description:Babesiosis among humans is on the rise in North America. Current diagnostic assays for the screening of babesiosis require blood collection by venipuncture, which is an invasive method. Urine on the other hand is a desirable biospecimen for biomarker analysis of Babesia microti infections because it can be collected periodically and non-invasively. Our group uses a new class of biomarker harvesting nanocage technology, which, when combined with mass spectrometry (MS), can determine the presence of parasite proteins shed in different bodily fluids of mammalian hosts, including urine. Using the hamster model of babesiosis, our nanoparticle-MS approach identified several B. microti proteins in erythrocytes, plasma, and urine samples. Surface and secreted antigens previously shown to elicit host immune responses against the parasite were particularly abundant in erythrocytes and plasma compared to other proteins. Two of these antigens, BmSA1 and BMR1_03g00947, showed different localization patterns by immunofluorescence of infected erythrocytes. Hamster urine samples from parasitemic animals harbored lower numbers of B. microti proteins compared to erythrocytes and plasma, with glycolytic enzymes, cytoskeletal components, and chaperones being the most frequently detected proteins. By applying novel nanoparticle-MS methods, a high level of analytical sensitivity can be achieved to detect multiple B. microti proteins in blood and urine. This is generally difficult to obtain with other techniques due to the masking of parasite biomarkers by the complex biomolecular matrix of bodily fluids from the host.

| S-EPMC9215174 | biostudies-literature

Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria.

Project description:BACKGROUND: Plasmodium falciparum infections could lead to severe malaria, principally in non-immune individuals as children and travellers from countries exempted of malaria. Severe malaria is often associated with the sequestration of P. falciparum-infected erythrocytes in deep micro-vascular beds via interactions between host endothelial receptors and parasite ligands expressed on the surface of the infected erythrocyte. Although, serological responses from individuals living in endemic areas against proteins expressed at surface of the infected erythrocyte have been largely studied, seldom data are available about the specific targets of antibody response from travellers. METHODS: In order to characterize antigens recognized by traveller sera, a comparison of IgG immune response against membrane protein extracts from uninfected and P. falciparum-infected red blood cells (iRBC), using immunoblots, was performed between non exposed individuals (n = 31) and briefly exposed individuals (BEI) (n = 38) to malaria transmission. RESULTS: Immune profile analysis indicated that eight protein bands from iRBC were significantly detected more frequently in the BEI group. Some of these antigenic proteins were identified by an original immuno-proteomic approach. CONCLUSION: Collectively, these data may be useful to characterize the singular serological immune response against a primary malaria infection in individuals briefly exposed to transmission.

| S-EPMC2959075 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data