Profiling -irradiated invasive Plasmodium falciparum merozoites using a systems biology approach

Plasmodium falciparum malaria severely impacts human health. In order to broaden our understanding of merozoite invasion of erythrocytes which is responsible for clinical disease, a P. falciparum -irradiated "long-lived merozoite" (LLM) line was investigated. Cell-sieve purified LLM invaded human erythrocytes with an improved efficiency of 10- to 300-fold greater than wild-type (WT) parasites. A comparison of their genomes identified limited changes in the open reading frame of LLM; while only marginal differences were observed in the transcriptomes. Analysis of their proteomes by quantitative mass-spectrometry identified 446 out of 981 proteins of known or unknown function with a significant change in protein abundance (ANOVA p < 0.05). Furthermore, the relative molar concentration of nearly 1100 merozoite proteins was established. Unfortunately, a specific change being responsible for the LLM phenotype was not identified. However, immunoblot analyses of LLM lysates showed proteolytic processing of some proteins of the MSP1 complex and AMA1 were delayed, suggesting that this delayed proteolysis positively impacted merozoite viability and subsequent invasion.

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Kumar K, Srinivasan P, Nold MJ, Moch JK, Reiter K, Sturdevant D, Otto TD, Squires RB, Herrera R, Nagarajan V, Rayner JC, Porcella SF, Geromanos SJ, Haynes JD, Narum DL