scholarly journals Protein prenylation and Hsp40 in thermotolerance of Plasmodium falciparum malaria parasites

2019 ◽  
Author(s):  
Emily S. Mathews ◽  
Andrew J. Jezewski ◽  
Audrey R. Odom John
Keyword(s):  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria ◽  
Complex Life Cycle ◽  
Protein Prenylation ◽  
Membrane Attachment ◽  
Client Proteins ◽  
Essential Function ◽  
And Function

AbstractDuring its complex life cycle, the malaria parasite survives dramatic changes in environmental temperature. Protein prenylation is required during asexual replication of Plasmodium falciparum, and heat shock protein 40 (HSP40; PF3D7_1437900) is post-translationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation of Hsp40 orthologs controls its localization and function, including temperature stress survival. In this work, we find that plastidial isopentenyl pyrophosphate (IPP) synthesis and protein farnesylation are required for malaria parasite survival after cold and heat shock. Furthermore, loss of HSP40 farnesylation alters its membrane attachment and interaction with proteins involved in crucial biological processes, such as glycolysis and cytoskeletal organization. Together, this work reveals that farnesylation of HSP40 in P. falciparum is a novel essential function of plastidial isoprenoid biosynthesis. We propose a model by which farnesyl-HSP40 promotes parasite thermotolerance and facilitates vesicular trafficking through its interaction with client proteins.

scholarly journals Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites

mBio ◽  
2021 ◽  
Author(s):  
Emily S. Mathews ◽  
Andrew J. Jezewski ◽  
Audrey R. Odom John
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria ◽  
Complex Life Cycle ◽  
Large Temperature ◽  
Protein Prenylation ◽  
Content Type

During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum , and the canonical heat shock protein 40 protein (HSP40; PF3D7_1437900) is posttranslationally modified with a 15-carbon farnesyl isoprenyl group.

scholarly journals Structure and Function of the Proteasome Activator PA28 of the Malaria Parasite Plasmodium falciparum

2019 ◽  
Vol 25 (S2) ◽  
pp. 1324-1325
Author(s):  
Riley Metcalf ◽  
Eric Hanssen ◽  
Stanley C. Xie ◽  
David Gillett ◽  
Andrew Leis ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Structure And Function ◽  
Proteasome Activator ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
And Function

scholarly journals Mouse model for exoerythrocytic stages of Plasmodium falciparum malaria parasite.

1992 ◽  
Vol 89 (9) ◽  
pp. 3701-3705 ◽  
Author(s):  
J. B. Sacci ◽  
M. E. Schriefer ◽  
J. H. Resau ◽  
R. A. Wirtz ◽  
L. J. Detolla ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mouse Model ◽  
Falciparum Malaria ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria

scholarly journals Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite

2012 ◽  
Vol 109 (32) ◽  
pp. 13052-13057 ◽  
Author(s):  
D. J. Park ◽  
A. K. Lukens ◽  
D. E. Neafsey ◽  
S. F. Schaffner ◽  
H.-H. Chang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria

scholarly journals Quantifying connectivity between local Plasmodium falciparum malaria parasite populations using identity by descent

PLoS Genetics ◽  
2017 ◽  
Vol 13 (10) ◽  
pp. e1007065 ◽  
Author(s):  
Aimee R. Taylor ◽  
Stephen F. Schaffner ◽  
Gustavo C. Cerqueira ◽  
Standwell C. Nkhoma ◽  
Timothy J. C. Anderson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Malaria Parasite ◽  
Plasmodium Falciparum Malaria ◽  
Identity By Descent ◽  
Parasite Populations

scholarly journals The Clp System in Malaria Parasites Degrades Essential Substrates to Regulate Plastid Biogenesis

2019 ◽  
Author(s):  
A. Florentin ◽  
D.R. Stephens ◽  
C.F. Brooks ◽  
R.P. Baptista ◽  
V Muralidharan
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Parasite ◽  
Affinity Purification ◽  
Nuclear Genome ◽  
Clp Protease ◽  
Complex Composition ◽  
Malaria Parasites ◽  
Human Malaria Parasite ◽  
Essential Function ◽  
Comprehensive Study

AbstractThe human malaria parasite, Plasmodium falciparum, contains an essential plastid called the apicoplast. Most of apicoplast proteins are encoded by the nuclear genome and it is unclear how the plastid proteome is regulated. Here, we study an apicoplast-localized caseinolytic-protease (Clp) system and how it regulates organelle proteostasis. Using null and conditional mutants, we demonstrated that the Clp protease (PfClpP) has robust enzymatic activity that is essential for apicoplast biogenesis. We developed a CRISPR/Cas9 based system to express catalytically-dead PfClpP, which showed that PfClpP oligomerizes as a zymogen and matured via trans-autocatalysis. The expression of a Clp chaperone (PfClpC) mutant led to the discovery of a functional chaperone-protease interaction essential for plastid function. Conditional mutants of the substrate-adaptor (PfClpS) demonstrated its essential function in plastid biogenesis. A combination of multiple affinity purification screens identified the Clp complex composition as well as putative Clp substrates. This comprehensive study reveals the molecular composition and interactions influencing the proteolytic function of the apicoplast Clp system and demonstrates its central role in the biogenesis of the plastid in malaria parasites.

scholarly journals Modulation of the expression of sirtuins and var genes by heat shock in the malaria parasite Plasmodium falciparum: a pattern emerges

2021 ◽  
Author(s):  
Linda O. Anagu ◽  
David R. Hulse ◽  
Paul D. Horrocks ◽  
Srabasti J Chakravorty
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Heat Shock ◽  
Malaria Parasite ◽  
Severe Disease ◽  
Expression Patterns ◽  
Stress Factors ◽  
Virulence Gene Expression

Abstract Background: In the malaria parasite Plasmodium falciparum the expression of ‘var’ virulence genes is regulated through epigenetic mechanisms. Its sirtuin epigenetic regulators have a direct effect on var gene expression patterns, are increased in a laboratory strain of P. falciparum exposed to heat shock and are positively associated with fever. A Gambia study extended this association to blood lactate and var genes commonly expressed in severe malaria, and between PfSir2A and group B var. A Kenyan study extended this association to between PfSir2A and overall var transcript level. These observations suggest a mechanism through which stress phenotypes in the human host might be sensed via a parasite sirtuin, and virulence gene expression modulated accordingly. Methods: In vitro experiments were conducted using laboratory and recently-laboratory-adapted Kenyan isolates of P. falciparum to follow up the correlative findings of the field study. To investigate a potential cause-and-effect relationship between host stress factors and parasite gene expression, qPCR was used to measure the expression of sirtuins and var genes after highly synchronous cultured parasites had been exposed to 2h or 6h of heat shock at 40°C or elevated lactate.Results: Heat shock was shown to influence the expression of PfSir2B in the trophozoites, whereas exposure to lactate was not. After the ring stages were exposed to heat shock; sirtuins, severe-disease-associated upsA and upsB var genes and var genes in general were not altered. More biological replicate experiments will be needed to confirm our observations. Conclusions: This study demonstrates that heat stress in laboratory and recently-laboratory-adapted isolates of P. falciparum results in a small increase in PfSir2B transcripts in the trophozoite stages only. By contrast, the association between hyperlactataemia and sirtuin/var gene expression that was previously observed in vivo appears to be coincidental rather than causative.

“PLATELET COUNT” , DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE IN MALARIA PATIENTS

1969 ◽  
Vol 2 (2) ◽  
pp. 206-209
Author(s):  
Muhammad Tahir Khan ◽  
Asif Hussain Munir ◽  
Alamzeb ◽  
Ahmad Arsalan Tahir
Keyword(s):  
Plasmodium Falciparum ◽  
Platelet Count ◽  
Malaria Parasite ◽  
Complete Blood Count ◽  
Prognostic Significance ◽  
Case Series ◽  
Plasmodium Falciparum Malaria ◽  
Response To Therapy ◽  
Mortality And Morbidity ◽  
Case Series Study

Malaria continues to be a cause of high mortality and morbidity. It can cause anemia and thrombocytopenia.The mechanism of thrombocytopenia in malaria is probably the consequence of several factors.Experimental data and clinical studies have successively emphasized the role of immune factors and thedestruction or sequestration of platelets. Thrombocytopenia might be a useful indicator of malaria and canalso be used as a marker of response to therapy. This study was conducted to evaluate thrombocytopenia inthe patients suffering from acute plasmodium vivax and plasmodium falciparum malaria separately. OBJECTIVE: To evaluate the effect of malaria on platelet count. MATERIALS AND METHODS: This is an original descriptive case series study and was carried out inpathology department Khyber Teaching Hospital Peshawar over period of six months from 1 st June 2011 to30 December 2011 . Total of 200 malaria parasite positive patients were included in the study. These patientsshowed malaria parasite in their peripheral blood smear (thick and thin) stained with Giemsa stain. P.vivaxand P.falciparum positive cases were grouped separately. Complete blood count was done on automatichematology analyzer and Platelet count was noted. RESULTS: Out of 200 patient, 120 were males and 80 were females. 127 (63.5%) were plasmodium vivaxpositive and 73 (36.5%) were plasmodium falciparum positive. Amongst P. Vivax positive patients 62(48.81%) showed thrombocytopenia while amongst P. falciparum positive patients 40 (54.79%) showedthrombocytopenia. Thus thrombocytopenia is observed to be more common amongst P. falciparum positivepatients. CONCLUSION:Malaria parasite causes thrombocytopenia. KEYWORDS: Platelets, thrombocytopenia, malaria.

Large-scale growth of the Plasmodium falciparum malaria parasite in a wave bioreactor

2012 ◽  
Vol 42 (3) ◽  
pp. 215-220 ◽  
Author(s):  
John P. Dalton ◽  
Corine G. Demanga ◽  
Sarah J. Reiling ◽  
Juliane Wunderlich ◽  
Jenny W.L. Eng ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Falciparum Malaria ◽  
Malaria Parasite ◽  
Large Scale ◽  
Plasmodium Falciparum Malaria ◽  
Scale Growth ◽  
Wave Bioreactor
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