First data on cholesterol metabolism in Ornithodoros argasid ticks: Molecular and functional characterization of the N-terminal domain of Niemann-Pick C1 proteins

• DOI: 10.1016/j.ttbdis.2024.102382
• Publication Date: 2024-07-20T01:47:41Z
• Authors: Lucía de Dios-Blá...; Ana Laura Cano-Ar...; Ricardo Pérez-Sán...; María González-Sá...; Ana Oleaga
• Keywords: NPC1

Cholesterol is a molecule vital for tick physiology, but ticks cannot synthesize it and rely on dietary cholesterol. Therefore, proteins involved in cholesterol absorption transport, such as the Niemann-Pick type C1 domain-containing (NPC1) proteins, are promising targets anti-tick vaccine development. The aim of this study was to assess structure, function, protective efficacy NPC1 orthologues identified previously midgut transcriptomes argasid Ornithodoros erraticus moubata. For purpose, their corresponding cDNA coding sequences were cloned sequenced, secondary 3D structures predicted, function evaluated through RNAi-mediated gene knockdown vitro feeding blood supplemented with ezetimibe, which inhibits binding by proteins. Subsequently, recombinant form from O. moubata (rOmNPC1) tested rabbit trial. While inhibiting ezetimibe resulted up 77 % mortality adult moubata, vaccination rOmNPC1 decreased female reproductive performance terms number fertility laid eggs. This presents initial molecular functional insights into soft supports hypothesis that disrupting metabolism diminishes viability reproduction, rendering drugs or vaccines.