Author:
Lonardi Stefano,Singh Pallavi,Liang Qihua,Vydyam Pratap,Khabirova Eleonora,Fang Tiffany,Gihaz Shalev,Thekkiniath Jose,Munshi Muhammad,Abel Steven,Batugedara Gayani,Gupta Mohit,Lu Xueqing Maggie,Lenz Todd,Chakravarty Sakshar,Cornillot Emmanuel,Hu Yangyang,Ma Wenxiu,Gonzalez Luis Miguel,Sánchez Sergio,Montero Estrella,Estrada Karel,Sánchez-Flores Alejandro,Harb Omar S.,Le Roch Karine G.,Ben Mamoun Choukri
Abstract
AbstractBabesia species are tick-transmitted apicomplexan pathogens and the causative agents of babesiosis, a malaria-like disease of major medical and veterinary importance. Of the different species of Babesia reported so far, Babesia duncani causes severe to lethal infection in patients. Despite the highly virulent nature of this parasite and the risk it may pose as an emerging pathogen, little is known about its biology, metabolic requirements, and pathogenesis. B. duncani is unique among apicomplexan parasites that infect red blood cells in that it can be continuously cultured in vitro in human erythrocytes but can also infect mice leading to fulminant babesiosis infection and death. Here we have taken advantage of the recent advances in the propagation of this parasite in vitro and in vivo to conduct detailed molecular, genomic and transcriptomic analyses and to gain insights into its biology. We report the assembly, 3D structure, and annotation of the nuclear genome of this parasite as well as its transcriptomic profile and an atlas of its metabolism during its intraerythrocytic life cycle. Detailed examination of the B. duncani genome and comparative genomic analyses identified new classes of candidate virulence factors, suitable antigens for diagnosis of active infection, and several attractive drug targets. Translational analyses and efficacy studies identified highly potent inhibitors of B. duncani thus enriching the pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.
Publisher
Cold Spring Harbor Laboratory