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PubMed1987

Plasmodium berghei and Plasmodium chabaudi: a neutral endopeptidase in parasite extracts and plasma of infected animals.

By using a sensitive fluorometric method with Val-Leu-Gly-Arg-3-amino-9-ethylcarbazole (VLGR-AEC) as a substrate, two endopeptidase activities were identified in two fractions of Sephacryl S-200 gel filtration from soluble P. berghei and P. chabaudi extracts. Controls with normal mouse erythrocytes, with leukocytes, and with reticulocyte enriched blood and different washing procedures during the preparation of soluble P. berghei extracts showed that the MW greater than 200 kDa fraction was a contaminant from erythrocytes and exhibited an optimal pH activity of 8.2. In contrast, the fraction 130 kDa was related to P. berghei and P. chabaudi and exhibited an optimal pH activity of 7.4. The two enzyme activities were compared with eight different substrates. The parasite endopeptidase showed a strong activity with Val-Leu-Gly-Lys-AEC (VLGK-AEC) and Ser-Gly-Lys-AEC (SGK-AEC) as substrates; in contrast, the mouse host endopeptidase poorly cleaved the VLGK-AEC and did not cleave SGK-AEC. Presence of the hydrophobic benzyl group on serine reduced the hydrolizing properties of P. berghei endopeptidase: the reverse was observed with host endopeptidase. The hydrolysis of the N-polyhydroxyalcanoyl-VLGK-AEC substrate by the parasite neutral endopeptidase strongly increased with the schizogonic stage, as shown with synchronized P. chabaudi in mice. By its physiological pH and specificity the release of this enzyme in mouse plasma during the infection could be of interest in a peptidyl-drug strategy.

Animals↗
PubMed1991

Morphological characteristics of intracerebral arterioles in clinical (Plasmodium falciparum) and experimental (Plasmodium berghei) cerebral malaria.

Spastic constriction of intracerebral arterioles was identified in clinical (P. falciparum) and experimental (P. berghei) cerebral malaria. Morphological criteria were used to characterize pathologically spastic constriction of arterioles. The significance of spastic constriction of intracerebral arterioles for microcirculatory disturbance in relation to development of cerebral malaria is discussed.

Adult↗
PubMed1996

The large difference in infectivity for mice of Plasmodium berghei and Plasmodium yoelii sporozoites cannot be correlated with their ability to enter into hepatocytes.

Sporozoites of P. yoelii nigeriensis are 50-100-times more infective to mice than the strain NK65 of P. berghei. To study the mechanisms involved in this striking difference in the infectivity of these closely related species of malaria parasites, we have developed a quantitative PCR targeted to parasite-specific ribosomal RNA. Using this method, we detect RNA from a single sporozoite, and exo-erythorcytic forms of RNA in the livers of mice injected with 200 sporozoites. We find that 20 h after sporozoite injection, there is no significant difference between the amounts of P. berghei and P. yoelii rRNA in the livers of C57/BL6 mice, indicating that these two parasite species invade hepatocytes with similar efficiency. Between 20 and 40 h, however, P. yoelii RNA increases 11 times, while P. berghei RNA increases only 1.6 times. We conclude that the greater infectivity of P. yoelii sporozoites in these mice reflects, at least in part, their superior development in hepatocytes. These data provide for the first time in vivo evidence supporting the notion that species-specificity of malaria is not determined by mechanisms associated with sporozoite attachment and penetration into the hepatocytes.

Animals↗