Molecular Characterization of EmABP , an 2 Apolipoprotein A-I Binding Protein Secreted by the 3 Echinococcus multilocularis Metacestode 4 5 Running title : Echinococcus Apolipoprotein A-I Binding Protein 6 7 8

23 Cestodes are unable to synthesize de novo most of their own membrane lipids, including 24 cholesterol, and have to take them up from the host during an infection. The underlying 25 molecular mechanisms are so far unknown. Here we report the identification and characterization 26 of a novel gene, Emabp, which is expressed by larval stages and adults of the fox-tapeworm 27 Echinococcus multilocularis. The encoded protein, EmABP, displays significant homologies to 28 apolipoprotein A-I binding protein (AI-BP) of mammalian origin and to metazoan YjeF_N 29 domain proteins. Like mammalian AI-BP, EmABP carries an export-directing signal sequence 30 which is absent in predicted AI-BP orthologs from the related flatworms Schistosoma japonicum 31 and Schmidtea mediterranea. Using a specific antibody and immuno-precipitation techniques, we 32 demonstrate that EmABP is secreted into the extra-parasitic environment and into hydatid fluid of 33 in vitro cultivated metacestode vesicles. Furthermore, we show that apolipoprotein A-I (apoA-I), 34 a major constituent of cholesterol-transporting high density lipoproteins, is present in hydatid 35 fluid. By pull-down experiments, we demonstrate that recombinantly expressed, purified EmABP 36 interacts with purified human apoA-I and is able to precipitate apoA-I from human serum. Based 37 on these features, and on the suggested function of AI-BP in cholesterol transport in higher 38 eukaryotes, we propose a role of EmABP in cholesteroland lipid-uptake mechanisms of larval 39 E. multilocularis. 40 41 42