scholarly journals PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum

Cell Reports ◽  
2017 ◽  
Vol 21 (7) ◽  
pp. 1746-1756 ◽  
Author(s):  
Anat Florentin ◽  
David W. Cobb ◽  
Jillian D. Fishburn ◽  
Michael J. Cipriano ◽  
Paul S. Kim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Clp Protease ◽  
Protease Stability

scholarly journals PfClpC Is An Essential Clp Chaperone Required For Plastid Integrity And Clp Protease Stability In Plasmodium falciparum

2016 ◽  
Author(s):  
Anat Florentin ◽  
David W Cobb ◽  
Jillian D Fishburn ◽  
Michael J Cipriano ◽  
Paul S Kim ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Arrest ◽  
Parasite Line ◽  
Functional Interactions ◽  
Conditional Mutant ◽  
Caseinolytic Protease ◽  
Active Protease ◽  
Protease Stability ◽  
Essential Function ◽  
Conditional Inhibition

SummaryThe deadly malaria parasite, Plasmodium falciparum, contains a non-photosynthetic plastid known as the apicoplast, that functions to produce essential metabolites. Little is known about its biology or regulation, but drugs that target the apicoplast are clinically effective. Using phylogenetic analysis, we identified a putative complex of clp (caseinolytic protease) genes. We genetically targeted members of this complex and generated conditional mutants of the PfClpC chaperone and PfClpP protease and found that they co-localize in the apicoplast. Conditional inhibition of the PfClpC chaperone resulted in growth arrest and apicoplast loss, and was rescued by addition of the essential apicoplast-derived metabolite, IPP. Using a double conditional-mutant parasite line, we discovered that the chaperone activity is required to stabilize the active protease, revealing functional interactions. These data demonstrate the essential function of PfClpC in maintaining apicoplast integrity and its role in regulating the proteolytic activity of the Clp complex.

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.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

Platelet Hypersensitivity in Acute Malaria (Plasmodium falciparum) Infection in Man

1981 ◽  
Vol 46 (02) ◽  
pp. 547-549 ◽  
Author(s):  
E M Essien ◽  
M I Ebhota
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Infection ◽  
Light Transmission ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Wave Pattern ◽  
Falciparum Infection ◽  
Secondary Wave ◽  
Control Subjects ◽  
The Mean

SummaryDuring acute malaria infection, platelets in human platelet-rich plasma are hypersensitive to the addition of ADP between 1.0 uM and 5.0 uM, or adrenaline 0.11 uM as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 uM), 39.8 ± 27 (1SD), was significantly greater than the value in 6 controls (5.2±6.7 (1SD); t = 3, 51 P <0.005). A similar pattern of response was obtained with higher ADP concentrations (2.4,4.5 or 5.0 uM) in 22 patients and 20 control subjects (89.9±14.9% vs 77.8±16.5% (1SD) t = 2.45, P <0.02). Addition of 4.5 uM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls.Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 ± 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2±15.7 ng/ml; t = 13.44, P <0.002).

Durch Vektoren übertragene Erkrankungen

2018 ◽  
Vol 18 (05) ◽  
pp. 332-338
Author(s):  
C. Kleine ◽  
U. Ziegler ◽  
E.-M. Schwienhorst ◽  
A. Stich
Keyword(s):  
Plasmodium Falciparum ◽  
Sich Eine ◽  
Malaria Tropica

ZusammenfassungDer folgende Artikel fokussiert auf Erkrankungen, deren Erreger von Vektoren (Insekten, Spinnentieren) aktiv auf den Menschen übertragen werden. Sie spielen in tropischen und subtropischen Regionen der Erde eine erhebliche Rolle und sind auch im Rahmen der Differenzialdiagnose bei kranken Reiserückkehrern von großer Bedeutung. Am wichtigsten ist die Malaria, insbesondere die lebensbedrohliche Malaria tropica durch Plasmodium falciparum. Jede fieberhafte Erkrankung aus den Tropen erfordert eine zeitnahe Malaria-Diagnostik. Tropische Viruserkrankungen durch Dengue-, West-Nil-, Chikungunya- oder Zika-Viren haben sich in den vergangenen Jahrzehnten massiv ausgebreitet und stellen auch eine zunehmende Bedrohung für den europäischen Raum dar. Andere Vektor-übertragene Erkrankungen sind zwar von großer lokaler Relevanz in endemischen Regionen, aber als importierte Infektionen in Deutschland relativ selten. Bei der Betreuung der Patienten empfiehlt sich eine enge Kooperation mit Tropenmedizinern.

Prevalence of Plasmodium falciparum and Salmonella typhi Infection and Coinfection and Their Association With Fever in Northern Tanzania

2018 ◽  
Vol 2 (2) ◽  
pp. 147-155
Author(s):  
Jaffu Chilongola ◽  
Sophia Kombe ◽  
Pius Horumpende ◽  
Rebeka Nazareth ◽  
Elias Sabuni ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Salmonella Typhi ◽  
Northern Tanzania
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