Babesia duncani multi-omics identifies virulence factors and drug targets.

Autor: Singh P; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA., Lonardi S; Department of Computer Science and Engineering, University of California, Riverside, CA, USA. stelo@cs.ucr.edu., Liang Q; Department of Computer Science and Engineering, University of California, Riverside, CA, USA., Vydyam P; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA., Khabirova E; Department of Statistics, University of California, Riverside, CA, USA., Fang T; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA., Gihaz S; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA., Thekkiniath J; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA., Munshi M; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA., Abel S; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA., Ciampossin L; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA., Batugedara G; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA., Gupta M; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA., Lu XM; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA., Lenz T; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA., Chakravarty S; Department of Computer Science and Engineering, University of California, Riverside, CA, USA., Cornillot E; Institut de Biologie Computationnelle (IBC), and Institut de Recherche en Cancérologie de Montpellier (IRCM - INSERM U1194), Institut régional du Cancer Montpellier (ICM) and Université de Montpellier, Montpellier, France., Hu Y; Department of Computer Science and Engineering, University of California, Riverside, CA, USA., Ma W; Department of Statistics, University of California, Riverside, CA, USA., Gonzalez LM; Parasitology Reference and Research Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Sánchez S; Reference and Research Laboratory on Food and Waterborne Bacterial Infections, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Estrada K; Unidad Universitaria de Secuenciación Masiva y Bioinformática, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México., Sánchez-Flores A; Unidad Universitaria de Secuenciación Masiva y Bioinformática, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, México., Montero E; Parasitology Reference and Research Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain., Harb OS; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA., Le Roch KG; Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, USA. karinel@ucr.edu., Mamoun CB; Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA. choukri.benmamoun@yale.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2023 May; Vol. 8 (5), pp. 845-859. Date of Electronic Publication: 2023 Apr 13.
DOI: 10.1038/s41564-023-01360-8
Abstrakt: Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis.
(© 2023. The Author(s).)
Databáze: MEDLINE
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