A Metabolite-Based Resistance Mechanism Against Malaria
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1072019 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27830837_1.fastq.gz | Fastqsanger.gz | |||
| SRR27830837_2.fastq.gz | Fastqsanger.gz | |||
| SRR27830838_1.fastq.gz | Fastqsanger.gz | |||
| SRR27830838_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Severe presentations of malaria, arising from Plasmodium spp. infection, are often associated with accumulation of circulating bilirubin, a condition known as hyperbilirubinemia or jaundice of malaria. Whether this represents an adaptive or maladaptive response to Plasmodium spp. infection is not understood. Departing from the textbook view of hyperbilirubinemia reflecting a failure to excrete bilirubin, we demonstrate that bilirubin production by biliverdin reductase A (BLVRA) partakes in a host adaptive response to malaria. Genetic Blvra deletion exacerbated malaria mortality in mice; This was associated with a >10-fold increase in parasite burden, compared to control mice expressing BLVRA, which cleared the parasite and survived malaria. At concentrations in the range of jaundice of malaria, unconjugated bilirubin arrested the proliferation and killed asexual blood stages of the human-infective P. falciparum in vitro. This was associated with disruption of the parasite’s mitochondrion and food vacuole as well as with the accumulation of hemozoin in the parasite’s cytoplasm. Moreover, bilirubin inhibited hemozoin (β-hematin) synthesis in vitro, a vital heme-detoxifying pathway targeted by Quinoline-based antimalarial drugs such as chloroquine. In conclusion, hyperbilirubinemia represents an evolutionary conserved metabolite-based resistance mechanism against malaria.
2025-03-24 | GSE254821 | GEO
Project description:Cerebral malaria (CM) is one of the most severe complications of malaria infection. There is evidence that repeated parasite exposure promotes resistance against CM, as indicated by the low incidence of CM in adults in malaria-endemic regions. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, a microarray study done utilising the tractable Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth infection.
2019-02-19 | E-MTAB-5513 | biostudies-arrayexpress
Project description:Severe presentations of malaria emerge as parasites from Plasmodium spp. proliferate and lyse red blood cells (RBC), producing extracellular hemoglobin (HB). The heme prosthetic groups are released upon HB oxidation generating circulating labile heme. Here we asked whether scavenging of extracellular HB and/or labile heme, by haptoglobin (HP) and/or hemopexin (HPX), respectively, is protective against severe presentations of malaria. We found that circulating labile heme is an independent risk factor for cerebral and non-cerebral severe presentations of P. falciparum malaria. Labile heme was negatively correlated with HP and HPX, which were however, not risk factors for severe P. falciparum malaria. Genetic HP and/or HPX deletion in mice led to accumulation of labile heme in plasma and kidneys in response to Plasmodium (chabaudi chabaudi) infection. This was associated with increased mortality and acute kidney injury (AKI) in ageing but not adult mice, corroborated in P. falciparum malaria by a an inverse correlation between HPX and heme with serological markers of AKI. In conclusion, HP and HPX exert an age-dependent protective effect against malaria that counters the pathogenesis of AKI in mice and presumably in humans.
2024-01-30 | GSE253390 | GEO
Project description:The microbiota metabolite, phloroglucinol, confers long-term protection against inflammation
| PRJNA1032421 | ENA
Project description:Double-kill mechanism of artemisinin against Plasmodium
| PRJNA983399 | ENA
Project description:Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study. Antibody-dependent phagocytosis of both ring-infected and uninfected erythrocytes from parasite cultures was strongly correlated with protection. A surface proteomic analysis revealed the presence of merozoite proteins including erythrocyte binding antigen-175 and -140 on ring-infected and uninfected erythrocytes, providing an additional antibody-mediated protective mechanism for their activity beyond invasion-inhibition. Competition phagocytosis assays support the hypothesis that merozoite antigens are the key mediators of this functional activity. Targeting ring-stage parasites may contribute to the control of parasitaemia and prevention of clinical malaria.
2022-08-11 | PXD033964 | Pride
Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season.
2017-01-01 | GSE86308 | GEO
Project description:The mechanism by which artemisinin and its derivatives (ARTs) kill malaria parasites remains unclear. Haem or iron activates ARTs to produce free radicals that kill malaria parasites. However, adding iron or haem supply did not enhance, but instead attenuated, the antimalarial effect of ARTs, suggesting that the free-radical effect (FRE) is not the only antimalarial mechanism of ARTs. Here, through the single-cell RNA sequencing analysis of Plasmodium yoelii 17XNL and P. falciparum 3D7 in vivo and in vitro, we found that the sensitive stages to ARTs were associated with the expression of genes related to haem and iron (HI), DNA synthesis, antioxidation and the pentose-phosphate-pathway (PPP). Furthermore, the stages included an ART-sensitive cycle crucial for DNA synthesis that encompassed the release of iron through haem degradation to the activation of the PPP by iron. Additionally, the mechanism of haemozoin formation created a unique condition for interaction between ARTs and HI. In particular, HI can attenuate the antimalarial action of ARTs, strongly suggesting the existence of a HI-use-disturbance effect that combined with FRE to confer ARTs with a double-kill antimalarial mechanism different from the effect of iron chelators.
2024-06-08 | GSE234872 | GEO
Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. Vaccinees received 3 doses of 1.8 X 106 irradiated sporozoites. Efficacy was measured by challenged by controlled human malaria infections (CHMI), and against naturally occurring Pf Infections in Malian adults during the malaria transmission season
2022-08-20 | GSE211599 | GEO
Project description:Feeding with a ketonic diet confers complete protection against malaria
| PRJNA1145259 | ENA