The essential malaria protein PfCyRPA targets glycans to invade erythrocytes.

Plasmodium falciparum is a human-adapted apicomplexan parasite that causes the most dangerous form of malaria. P. falciparum cysteine-rich protective antigen (PfCyRPA) is an invasion complex protein essential for erythrocyte invasion. The precise role of PfCyRPA in this process has not been resolved. Here, we show that PfCyRPA is a lectin targeting glycans terminating with α2-6-linked N-acetylneuraminic acid (Neu5Ac). PfCyRPA has a >50-fold binding preference for human, α2-6-linked Neu5Ac over non-human, α2-6-linked N-glycolylneuraminic acid. PfCyRPA lectin sites were predicted by molecular modeling and validated by mutagenesis studies. Transgenic parasite lines expressing endogenous PfCyRPA with single amino acid exchange mutants indicated that the lectin activity of PfCyRPA has an important role in parasite invasion. Blocking PfCyRPA lectin activity with small molecules or with lectin-site-specific monoclonal antibodies can inhibit blood-stage parasite multiplication. Therefore, targeting PfCyRPA lectin activity with drugs, immunotherapy, or a vaccine-primed immune response is a promising strategy to prevent and treat malaria.

Temperature- versus precipitation-limitation shape local temperature tolerance in a Holarctic freshwater crustacean.

Species with wide geographical distributions are often adapted locally to the prevailing temperatures. To understand how they respond to ongoing climatic change, we must appreciate the interplay between temperature, seasonality and the organism's life cycle. The temperature experienced by many organisms results from an often-overlooked combination of climate and phenology. Summer-active (high latitude) populations are expected to adapt to local summer temperatures, but this is not expected for populations that outlive the summer in their dormant stage (low latitude, precipitation-limited). We recorded reproduction and survival in genotypes from 123 Holarctic populations of Daphnia magna during a multi-generation thermal ramp experiment. Genotypes from summer-active populations showed a positive relationship between heat tolerance and local summer temperature, whereas winter-active populations did not. These findings are consistent with the hypothesis that D. magna adapts to the local temperatures the animals experience during their planktonic phase. We conclude that predicting local temperature adaptation, in particular in the light of climate change, needs to consider the phenology of geographically wide-ranging species.