Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium.

During the blood meal of a Plasmodium-infected mosquito, 10 to 100 parasites are inoculated into the skin and a proportion of these migrate via the bloodstream to the liver where they infect hepatocytes. The Plasmodium liver stage, despite its clinical silence, represents a highly promising target for antimalarial drug and vaccine approaches. Successfully invaded parasites undergo a massive proliferation in hepatocytes, producing thousands of merozoites that are transported into a blood vessel to infect red blood cells. To successfully develop from the liver stage into infective merozoites, a tight regulation of gene expression is needed. Although this is a very interesting aspect in the biology of Plasmodium, little is known about gene regulation in Plasmodium parasites in general and in the liver stage in particular. We have functionally analyzed a novel promoter region of the rodent parasite Plasmodium berghei that is exclusively active during the liver stage of the parasite. To prove stage-specific activity of the promoter, GFP and luciferase reporter assays have been successfully established, allowing both qualitative and accurate quantitative analysis. To further characterize the promoter region, the transcription start site was mapped by rapid amplification of cDNA ends (5'-RACE). Using promoter truncation experiments and site-directed mutagenesis within potential transcription factor binding sites, we suggest that the minimal promoter contains more than one binding site for the recently identified parasite-specific ApiAP2 transcription factors. The identification of a liver stage-specific promoter in P. berghei confirms that the parasite is able to tightly regulate gene expression during its life cycle. The identified promoter region might now be used to study the biology of the Plasmodium liver stage, which has thus far proven problematic on a molecular level. Stage-specific expression of dominant-negative mutant proteins and overexpression of proteins normally active in other life cycle stages will help to understand the function of the proteins investigated.

Host-parasite relationships of the clover cyst nematode, Heterodera trifolii Goffart /

Cover title.

A new parasite on Gracilaria confervoides.

Type-written ms.

The animal parasite supposed to be the cause of yellow fever /

Cover title.

Report of Animal Disease and Parasite Research Branch, ARS, USDA. [Presented at the] fifth annual meeting of the North Central States Poultry Disease Conference, University of Wisconsin, Madison, Wisconsin, May 19 and 20, 1954.

Mimeographed.

Gracilariophila, a new parasite on Gracilaria confervoides.

Originally submitted in 1909 as thesis (M.S.) University of California.

The gid parasite (Coenurus cerebralis) : its presence in American sheep /

Mode of access: Internet.

Goniozus gallicola fouts, a parasite of moth larvae, with notes on other bethylids (Hymenoptera : Bethylidae, Lepidoptera : Gelechiidae) /

Issued Feb. 1976.

A host-parasite catalog of North American Tachinidae (Diptera) /

Issued June 1978.

Trypanosoma americanum : a common blood parasite of American cattle /

Bibliography: p. 39.

The gid parasite and allied species of the cestode genus Multiceps.

"October 10, 1910."

Bracon lissogaster Mues. : a parasite of the wheat stem sawfly /

Literature cited: p. 7.

La Chambre de Commerce de Saint-Etienne; Bustes & Portraits; Vingt-trois heliogravures de Felix Thiollier faites d'apres les originaux des pentures et sculptures appartenant a la Chambre de Commerce, oeuvres de Hte. Flandrin, Albert Maignan, Guillaume, Montagny, etc.

Mode of access: Internet.

Author notation in hte library of congress

Mode of access: Internet.

New haplotypes of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene among chloroquine-resistant parasite isolates

Mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene were examined to assess their associations with chloroquine resistance in clinical samples from Armopa (Papua) and Papua New Guinea. In Papua, two of the five pfcrt haplotypes found were new: SVIET from Armopa and CVIKT from an isolate in Timika. There was also a strong association (P < 0.0001) between the pfcrt 76T allele and chloroquine resistance in 50 samples. In Papua New Guinea, mutations in the pfcrt gene were observed in 15 isolates with chloroquine minimum inhibitory concentrations (MICs) of 16-64 pmol, while the remaining six isolates, which had a wild-type pfcrt gene at codon 76, had MICs of 2-8 pmol. These observations confirm that mutations at codon 76 in the pfcrt gene are present in both in vivo and in vitro cases of chloroquine resistance, and that detection of the pfcrt 76T allele could predict potential chloroquine treatment failures.