LaCount, D. J. et al. A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438, 103-107

Howard Hughes Medical Institute, University of Washington, Box 357730, Seattle, Washington 98195, USA.
Nature (Impact Factor: 42.35). 12/2005; 438(7064):103-7. DOI: 10.1038/nature04104
Source: PubMed

ABSTRACT Plasmodium falciparum causes the most severe form of malaria and kills up to 2.7 million people annually. Despite the global importance of P. falciparum, the vast majority of its proteins have not been characterized experimentally. Here we identify P. falciparum protein-protein interactions using a high-throughput version of the yeast two-hybrid assay that circumvents the difficulties in expressing P. falciparum proteins in Saccharomyces cerevisiae. From more than 32,000 yeast two-hybrid screens with P. falciparum protein fragments, we identified 2,846 unique interactions, most of which include at least one previously uncharacterized protein. Informatic analyses of network connectivity, coexpression of the genes encoding interacting fragments, and enrichment of specific protein domains or Gene Ontology annotations were used to identify groups of interacting proteins, including one implicated in chromatin modification, transcription, messenger RNA stability and ubiquitination, and another implicated in the invasion of host cells. These data constitute the first extensive description of the protein interaction network for this important human pathogen.

Download full-text


Available from: Sudhir Sahasrabudhe, Aug 20, 2015
  • Source
    • "Expression profiling data throughout the intraerythrocytic cycle (oligonucleotide-based microarrays in both glass slide and Affymetrix formats) as well as single nucleotide polymorphism (SNP) analysis for 20 P. falciparum strains and 100 P. falciparum isolates (Jeffares et al., 2007; Mu et al., 2007; Volkman et al., 2007) are also available. Additional functional data sets include evidence of protein–protein interactions (Y2H and predicted interactome) (LaCount et al., 2005; Date and Stoeckert, 2006); Genome Ontology (GO) (Ashburner et al., 2000) and InterPro domain (Mulder et al., 2005) annotations for P. falciparum, P. vivax, P. berghei, P. yoelii, P. knowlesi and P. chabaudi; Enzyme Commission (EC) number (Ashburner et al., 2000) annotations for P. falciparum, P. yoelii and P. knowlesi (Ginsburg, 2006); and metabolic pathway assignments for P. falciparum (Ginsburg, 2006). Predictions of protein subcellular localisation (Bendtsen et al., 2004) and transmembrane domains (Krogh et al., 2001) for P. falciparum, P. vivax, P. berghei, P. yoelii, P. knowlesi and P. chabaudi are available, as well as parasite-specific predictions (P. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccines are one of the most effective interventions to improve public health, however, the generation of highly effective vaccines for many diseases has remained difficult. Three chronic diseases that characterise these difficulties include malaria, tuberculosis and HIV, and they alone account for half of the global infectious disease burden. The whole organism vaccine approach pioneered by Jenner in 1796 and refined by Pasteur in 1857 with the "isolate, inactive and inject" paradigm has proved highly successful for many viral and bacterial pathogens causing acute disease but has failed with respect to malaria, tuberculosis and HIV as well as many other diseases. A significant advance of the past decade has been the elucidation of the genomes, proteomes and transcriptomes of many pathogens. This information provides the foundation for new 21(st) Century approaches to identify target antigens for the development of vaccines, drugs and diagnostic tests. Innovative genome-based vaccine strategies have shown potential for a number of challenging pathogens, including malaria. We advocate that genome-based rational vaccine design will overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued vaccine developers for many years.
    International Journal for Parasitology 09/2014; 44(12). DOI:10.1016/j.ijpara.2014.07.010 · 3.40 Impact Factor
  • Source
    • "Consequently, constructing PPI networks is especially meaningful for understanding many physiological, pathological and developmental processes for almost all species. Various high-throughput experimental approaches and computational methods have been performed to predict and analyze PPI networks in many species, such as Saccharomyces cerevisiae (Schwikowski et al., 2000), Drosophila melanogaster (Giot et al., 2003), Caenorhabditis elegans (Li et al., 2004), Plasmodium falciparum (LaCount et al., 2005), Campylobacter jejuni (Parrish et al., 2007), Escherichia coli (Butland et al., 2005), Helicobacter pylori (Rain et al., 2001) and Leptospira interrogans (Sun et al., 2006). The application of high-throughput experimental methods, such as yeast two-hybrid system (Y2H), mass spectrometry (MS), protein microarrays and tandem affinity purification (TAP) have generated a large amount of PPIs in many species (Raman, 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Xanthomonas oryzae pv. oryzae (Xoo), the causal agent of bacterial blight disease in rice, is one of the most serious plant pathogens worldwide. In the current analysis, we constructed a protein-protein interaction network of Xoo strain PXO99(A) with two computational approaches (interolog method and domain combination method), and verified by K-Nearest Neighbor classification method. The predicted PPI network of Xoo PXO99(A) contains 36,886 interactions among 1,988 proteins. KNN verification and GO annotation confirm the reliability of the network. Detailed analysis of flagellar synthesis and chemotaxis system shows that σ factors (especially σ(28), σ(54)) in Xoo PXO99(A) are very important for flagellar synthesis and motility, and transcription factors RpoA, RpoB and RpoC are hubs to connect most σ factors. Furthermore, Xoo PXO99(A) may have both cAMP and c-di-GMP signal transduction system, and the latter is especially important for this plant pathogen. This study therefore provides valuable clues to explore the pathogenicity and metabolic regulation of Xoo PXO99(A).
    Research in Microbiology 10/2013; 164. DOI:10.1016/j.resmic.2013.09.001 · 2.83 Impact Factor
  • Source
    • "The first P. falciparum genome was published in 2002, P. vivax and P. knowlesi in 2008 and P. cynomolgi just recently (Carlton et al., 2008a; Gardner et al., 2002; Pain et al., 2008; Tachibana et al., 2012); these type of strains have been followed by the availability of sequences from many other P. falciparum genomes and a number of P. vivax genomes, especially since NextGen sequencing has amplified what is possible and brought down the timeframe and cost (Chan et al., 2012). Functional genomics u shered in the " omics " era, with emphasis moving from in vitro to ex vivo transcriptomes and proteomes for P. falciparum (Daily et al., 2007; Dharia et al., 2010; Kuss et al., 2012; LaCount et al., 2005; Lasonder et al., 2002, 2008) and recently initial P. vivax transcriptomes (Bozdech et al., 2008; Westenberger et al., 2010) and proteomes (Acharya et al., 2009, 2011; Roobsoong et al., 2010; Roobsoong et al., 2011) based on clinical samples. We have been complementing such data with parasites generated in NHP infections initiated from P. vivax adapted and simian malaria parasite cryo-preserved stocks, from which we can obtain multiple biological replicates of stage-specific samples (Lapp et al., unpublished data). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Plasmodium vivax has unique attributes to support its survival in varying ecologies and climates. These include hypnozoite forms in the liver, an invasion preference for reticulocytes, caveola-vesicle complex structures in the infected erythrocyte membrane and rapidly forming and circulating gametocytes. These characteristics make this species very different from P. falciparum. Plasmodium cynomolgi and other related simian species have identical biology and can serve as informative models of P. vivax infections. Plasmodium vivax and its model parasites can be grown in non-human primates (NHP), and in short-term ex vivo cultures. For P. vivax, in the absence of in vitro culture systems, these models remain highly relevant side by side with human clinical studies. While post-genomic technologies allow for greater exploration of P. vivax-infected blood samples from humans, these come with restrictions. Two advantages of NHP models are that infections can be experimentally tailored to address hypotheses, including genetic manipulation. Also, systems biology approaches can capitalise on computational biology combined with set experimental infection periods and protocols, which may include multiple sampling times, different types of samples, and the broad use of "omics" technologies. Opportunities for research on vivax malaria are increasing with the use of existing and new methodological strategies in combination with modern technologies.
    Advances in Parasitology 01/2013; 81:1-26. DOI:10.1016/B978-0-12-407826-0.00001-1 · 4.36 Impact Factor
Show more