Protozoan Proteins

Publication Title: 
European Journal of Immunology

Antibodies (Abs) are critical for immunity to malaria. However, Plasmodium falciparum specific Abs decline rapidly in absence of reinfection, suggesting impaired immunological memory. This study determines whether residents of Sweden that were treated for malaria following international travel maintained long-lasting malaria-specific Abs and memory B cells (MBCs).

Author(s): 
Ndungu, Francis M.
Lundblom, Klara
Rono, Josea
Illingworth, Joseph
Eriksson, Sara
F‰rnert, Anna
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Macronuclear telomeres in Oxytricha exist as DNA-protein complexes in which the termini of the G-rich strands are bound by a 97-kDa telomere protein. During telomeric DNA replication, the replication machinery must have access to the G-rich strand. However, given the stability of telomere protein binding, it has been unclear how this is accomplished. In this study we investigated the ability of several different DNA polymerases to access telomeric DNA in Oxytricha telomere protein-DNA complexes.

Author(s): 
Shippen, D. E.
Blackburn, E. H.
Price, C. M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Macronuclear telomeres in Oxytricha exist as DNA-protein complexes in which the termini of the G-rich strands are bound by a 97-kDa telomere protein. During telomeric DNA replication, the replication machinery must have access to the G-rich strand. However, given the stability of telomere protein binding, it has been unclear how this is accomplished. In this study we investigated the ability of several different DNA polymerases to access telomeric DNA in Oxytricha telomere protein-DNA complexes.

Author(s): 
Shippen, D. E.
Blackburn, E. H.
Price, C. M.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes telomeric DNA. A pseudoknot structure is phylogenetically conserved within the RNA component of telomerase in all ciliated protozoans examined. Here, we report that disruptions of the pseudoknot base pairing within the telomerase RNA from Tetrahymena thermophila prevent the stable assembly in vivo of an active telomerase. Restoring the base-pairing potential of the pseudoknot by compensatory changes restores telomerase activity to essentially wild-type levels.

Author(s): 
Gilley, D.
Blackburn, E. H.
Publication Title: 
Trends in Parasitology

The outcome of the Phase IIb trial of RTS,S (a vaccine comprising the polypeptides RTS and S) in young Mozambican children consolidated hopes that effective vaccination against malaria is a step nearer, and even elicited a generous promise of commitment from the Chancellor of the Exchequer of the UK. However, it seems that both optimism and generosity should be moderated by the failure of this vaccine to induce meaningful protection against infection by Plasmodium falciparum and that we should await confirmation of its efficacy in diminishing the incidence of severe malaria.

Author(s): 
Snounou, Georges
Gr¸ner, Anne Charlotte
M¸ller-Graf, Christine D. M.
Mazier, Dominique
Renia, Laurent
Publication Title: 
Antimicrobial Agents and Chemotherapy

The endoperoxides are a new class of antimalarial agents, of which artemisinin (qinghaosu) is the prototype. We have previously shown that artemisinin is capable of alkylating proteins in model reactions. In the present study, we showed that when Plasmodium falciparum-infected erythrocytes are treated with a radiolabeled antimalarial endoperoxide, either arteether, dihydroartemisinin, or Ro 42-1611 (arteflene), the radioactivity is largely coverted into a form which can be extracted with sodium dodecyl sulfate (SDS).

Author(s): 
Asawamahasakda, W.
Ittarat, I.
Pu, Y. M.
Ziffer, H.
Meshnick, S. R.
Publication Title: 
Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America

The inability to distinguish failures of treatment of Plasmodium falciparum infection from new infections is an important impediment to the evaluation of antimalarial drugs. On the basis of a pilot study utilizing polymerase chain reaction (PCR) single-strand conformational polymorphism (SSCP) analysis to genotype P. falciparum isolates, we sought to confirm that PCR SSCP analysis could reliably distinguish infections for which treatment failed from unrelated infections with a sample size adequate to estimate the accuracy of this technique.

Author(s): 
Ohrt, C.
Mirabelli-Primdahl, L.
Looareesuwan, S.
Wilairatana, P.
Walsh, D.
Kain, K. C.
Publication Title: 
Blood

Ring-infected erythrocyte surface antigen (RESA)-positive, Plasmodium falciparum-negative red blood cells (RBCs) are cells from which the malaria parasite has been removed by the host without the destruction of the erythrocyte ("pitting"). The survival of RESA-RBCs in vivo was assessed in 14 severe and 6 uncomplicated falciparum malaria patients.

Author(s): 
Newton, P. N.
Chotivanich, K.
Chierakul, W.
Ruangveerayuth, R.
Teerapong, P.
Silamut, K.
Looareesuwan, S.
White, N. J.
Publication Title: 
Antimicrobial Agents and Chemotherapy

Artemisinin and its derivatives are endoperoxide-containing antimalarial drugs that appear to form adducts in situ with the Plasmodium falciparum translationally controlled tumor protein (TCTP) homolog. Immunoprecipitation with antibody to recombinant TCTP suggests that adducts may form with both monomeric and dimeric TCTP.

Author(s): 
Bhisutthibhan, J.
Meshnick, S. R.
Publication Title: 
The Journal of Infectious Diseases

In acute malaria, red blood cells (RBCs) that have been parasitized, but no longer contain a malaria parasite, are found in the circulation (ring-infected erythrocyte surface antigen [RESA]-RBCs). These are thought to arise by splenic removal of dead or damaged intraerythrocytic parasites and return of the intact RBCs to the circulation.

Author(s): 
Chotivanich, Kesinee
Udomsangpetch, Rachanee
McGready, Rose
Proux, Stephane
Newton, Paul
Pukrittayakamee, Sasithon
Looareesuwan, Sornchai
White, Nicholas J.

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