Data Entry: Please note that the research database will be replaced by UNIverse by the end of October 2023. Please enter your data into the system https://universe-intern.unibas.ch. Thanks
A lipocalin mediates unidirectional haem biomineralization in malaria parasites
Discussion paper / Internet publication
ID
4662519
Digital Object Identifier DOI
10.1101/2020.02.18.954289
Author(s)
Matz, Joachim M.; Drepper, Benjamin; Blum, Thorsten B.; van Genderen, Eric; Burrell, Alana; Martin, Peer; Stach, Thomas; Collinson, Lucy; Abrahams, Jan Pieter; Matuschewski, Kai; Blackman, Michael J.
A lipocalin mediates unidirectional haem biomineralization in malaria parasites
Series title
bioRxiv
Publisher / Institution
bioRxiv
Abstract
During blood stage development, malaria parasites are challenged with the detoxification of enormous amounts of haem released during the proteolytic catabolism of erythrocytic haemoglobin. They tackle this problem by sequestering haem into bioinert crystals known as haemozoin. The mechanisms underlying this biomineralization process remain enigmatic. Here, we demonstrate that both rodent and human malaria parasite species secrete and internalize a lipocalin-like protein, PV5, to control haem crystallization. Transcriptional deregulation of PV5 in the rodent parasite Plasmodium berghei results in inordinate elongation of haemozoin crystals, while conditional PV5 inactivation in the human malaria agent Plasmodium falciparum causes excessive multi-directional crystal branching. Although haemoglobin processing remains unaffected, PV5-deficient parasites generate less haemozoin. Electron diffraction analysis indicates that despite the distinct changes in crystal morphology neither the crystalline order nor unit cell of haemozoin are affected by impaired PV5 function. Deregulation of PV5 expression renders P. berghei hypersensitive to the antimalarial drugs artesunate, chloroquine, and atovaquone, resulting in accelerated parasite clearance following drug treatment in vivo . Together, our findings demonstrate the Plasmodium -tailored role of a lipocalin family member in haemozoin formation and underscore the haem biomineralization pathway as an attractive target for therapeutic exploitation.