scholarly journals Revealing mechanisms underlying variation in malaria virulence: effective propagation and host control of uninfected red blood cell supply

2012 ◽  
Vol 9 (76) ◽  
pp. 2804-2813 ◽  
Author(s):  
C. J. E. Metcalf ◽  
G. H. Long ◽  
N. Mideo ◽  
J. D. Forester ◽  
O. N. Bjørnstad ◽  
...  
Keyword(s):  
Blood Cell ◽  
Statistical Methods ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Trade Off ◽  
Transmission Rates ◽  
Fitness Consequences ◽  
Self Harm ◽  
Using Data ◽  
Self Defence

Malaria parasite clones with the highest transmission rates to mosquitoes also tend to induce the most severe fitness consequences (or virulence) in mammals. This is in accord with expectations from the virulence–transmission trade-off hypothesis. However, the mechanisms underlying how different clones cause virulence are not well understood. Here, using data from eight murine malaria clones, we apply recently developed statistical methods to infer differences in clone characteristics, including induction of differing host-mediated changes in red blood cell (RBC) supply. Our results indicate that the within-host mechanisms underlying similar levels of virulence are variable and that killing of uninfected RBCs by immune effectors and/or retention of RBCs in the spleen may ultimately reduce virulence. Furthermore, the correlation between clone virulence and the degree of host-induced mortality of uninfected RBCs indicates that hosts increasingly restrict their RBC supply with increasing intrinsic virulence of the clone with which they are infected. Our results demonstrate a role for self-harm in self-defence for hosts and highlight the diversity and modes of virulence of malaria.

scholarly journals Plasmodium falciparum erythrocyte-binding antigen 175 triggers a biophysical change in the red blood cell that facilitates invasion

2017 ◽  
Vol 114 (16) ◽  
pp. 4225-4230 ◽  
Author(s):  
Marion Koch ◽  
Katherine E. Wright ◽  
Oliver Otto ◽  
Maik Herbig ◽  
Nichole D. Salinas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Blood Cell ◽  
Signaling Pathways ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Red Cell ◽  
Biophysical Properties ◽  
Parasite Invasion ◽  
Bending Modulus ◽  
Erythrocyte Binding

Invasion of the red blood cell (RBC) by the Plasmodium parasite defines the start of malaria disease pathogenesis. To date, experimental investigations into invasion have focused predominantly on the role of parasite adhesins or signaling pathways and the identity of binding receptors on the red cell surface. A potential role for signaling pathways within the erythrocyte, which might alter red cell biophysical properties to facilitate invasion, has largely been ignored. The parasite erythrocyte-binding antigen 175 (EBA175), a protein required for entry in most parasite strains, plays a key role by binding to glycophorin A (GPA) on the red cell surface, although the function of this binding interaction is unknown. Here, using real-time deformability cytometry and flicker spectroscopy to define biophysical properties of the erythrocyte, we show that EBA175 binding to GPA leads to an increase in the cytoskeletal tension of the red cell and a reduction in the bending modulus of the cell’s membrane. We isolate the changes in the cytoskeleton and membrane and show that reduction in the bending modulus is directly correlated with parasite invasion efficiency. These data strongly imply that the malaria parasite primes the erythrocyte surface through its binding antigens, altering the biophysical nature of the target cell and thus reducing a critical energy barrier to invasion. This finding would constitute a major change in our concept of malaria parasite invasion, suggesting it is, in fact, a balance between parasite and host cell physical forces working together to facilitate entry.

scholarly journals A multifunctional serine protease primes the malaria parasite for red blood cell invasion

2009 ◽  
Vol 28 (6) ◽  
pp. 725-735 ◽  
Author(s):  
Konstantinos Koussis ◽  
Chrislaine Withers-Martinez ◽  
Sharon Yeoh ◽  
Matthew Child ◽  
Fiona Hackett ◽  
...  
Keyword(s):  
Blood Cell ◽  
Serine Protease ◽  
Cell Invasion ◽  
Red Blood Cell ◽  
Malaria Parasite

scholarly journals Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor

2017 ◽  
Vol 21 (6) ◽  
pp. 731-741.e10 ◽  
Author(s):  
Joana Mendonca Santos ◽  
Gabrielle Josling ◽  
Philipp Ross ◽  
Preeti Joshi ◽  
Lindsey Orchard ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Blood Cell ◽  
Cell Invasion ◽  
Red Blood Cell ◽  
Malaria Parasite

scholarly journals PS1205 META-ANALYSIS USING DATA OF RED BLOOD CELL ENZYME ASSAY AND PROTEOME IN PATIENTS WITH DIAMOND-BLACKFAN ANEMIA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 549
Author(s):  
T. Utsugisawa ◽  
T. Uchiyama ◽  
T. Aoki ◽  
A. Kinoshita ◽  
Y. Okamoto ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Enzyme Assay ◽  
Meta Analysis ◽  
Diamond Blackfan Anemia ◽  
Cell Enzyme ◽  
Using Data

scholarly journals Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-Specific Organelles in Plasmodium falciparum

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Sabrina Absalon ◽  
Karin Blomqvist ◽  
Rachel M. Rudlaff ◽  
Travis J. DeLano ◽  
Michael P. Pollastri ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Protein Kinase ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Dependent Protein Kinase ◽  
Calcium Dependent ◽  
Dependent Protein ◽  
Parasite Egress ◽  
Calcium Dependent Protein Kinase

ABSTRACT The human malaria parasite Plasmodium falciparum requires efficient egress out of an infected red blood cell for pathogenesis. This egress event is highly coordinated and is mediated by several signaling proteins, including the plant-like P. falciparum calcium-dependent protein kinase 5 (PfCDPK5). Knockdown of PfCDPK5 results in an egress block where parasites are trapped inside their host cells. The mechanism of this PfCDPK5-dependent block, however, remains unknown. Here, we show that PfCDPK5 colocalizes with a specialized set of parasite organelles known as micronemes and is required for their discharge, implicating failure of this step as the cause of the egress defect in PfCDPK5-deficient parasites. Furthermore, we show that PfCDPK5 cooperates with the P. falciparum cGMP-dependent kinase (PfPKG) to fully activate the protease cascade critical for parasite egress. The PfCDPK5-dependent arrest can be overcome by hyperactivation of PfPKG or by physical disruption of the arrested parasite, and we show that both treatments facilitate the release of the micronemes required for egress. Our results define the molecular mechanism of PfCDPK5 function and elucidate the complex signaling pathway of parasite egress. IMPORTANCE The signs and symptoms of clinical malaria result from the replication of parasites in human blood. Efficient egress of the malaria parasite Plasmodium falciparum out of an infected red blood cell is critical for pathogenesis. The P. falciparum calcium-dependent protein kinase 5 (PfCDPK5) is essential for parasite egress. Following PfCDPK5 knockdown, parasites remain trapped inside their host cell and do not egress, but the mechanism for this block remains unknown. We show that PfCDPK5 colocalizes with parasite organelles known as micronemes. We demonstrate that PfCDPK5 is critical for the discharge of these micronemes and that failure of this step is the molecular mechanism of the parasite egress arrest. We also show that hyperactivation of the cGMP-dependent kinase PKG can overcome this arrest. Our data suggest that small molecules that inhibit the egress signaling pathway could be effective antimalarial therapeutics.

scholarly journals Time-Lapse Imaging of Red Blood Cell Invasion by the Rodent Malaria Parasite Plasmodium yoelii

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e50780 ◽  
Author(s):  
Kazuhide Yahata ◽  
Moritz Treeck ◽  
Richard Culleton ◽  
Tim-Wolf Gilberger ◽  
Osamu Kaneko
Keyword(s):  
Blood Cell ◽  
Cell Invasion ◽  
Red Blood Cell ◽  
Malaria Parasite ◽  
Time Lapse ◽  
Plasmodium Yoelii ◽  
Rodent Malaria Parasite ◽  
Rodent Malaria ◽  
Parasite Plasmodium ◽  
Time Lapse Imaging
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