The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host’s liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood. Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite’s glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.

Staphylococcus aureus is an important model organism and pathogen. This S. aureus proteome overview details shared and specific proteins and selected virulence-relevant protein complexes from representative strains of all three major clades. To determine the strain distribution and major clades we used a refined strain comparison combining ribosomal RNA, MLST markers, and looking at highly-conserved regions shared between strains. This analysis shows three sub-clades (A–C) for S. aureus. As calculations are complex and strain annotation is quite time consuming we compare here key representatives of each clade with each other: model strains COL, USA300, Newman, and HG001 (clade A), model strain N315 and Mu50 (clade B) and ED133 and MRSA252 (clade C). We look at these individual proteomes and compare them to a background of 64 S. aureus strains. There are overall 13,284 S. aureus proteins not part of the core proteome which are involved in different strain-specific or more general complexes requiring detailed annotation and new experimental data to be accurately delineated. By comparison of the eight representative strains, we identify strain-specific proteins (e.g., 18 in COL, 105 in N315 and 44 in Newman) that characterize each strain and analyze pathogenicity islands if they contain such strain-specific proteins. We identify strain-specific protein repertoires involved in virulence, in cell wall metabolism, and phosphorylation. Finally we compare and analyze protein complexes conserved and well-characterized among S. aureus (a total of 103 complexes), as well as predict and analyze several individual protein complexes, including structure modeling in the three clades.