Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of theileria-induced leukocyte transformation
Microsoft Excel 2007
Supplemental File 1
Supplemental File 2
Supplemental File 3
Supplemental File 4
Supplemental File 5
Supplemental File 6
Supplemental File 7
Supplemental File 8
Supplemental File 9
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Computational Bioscience Research Center (CBRC)
Pathogen Genomics Laboratory
Online Publication Date2012-09-04
Print Publication Date2012-09-04
Permanent link to this recordhttp://hdl.handle.net/10754/325462
MetadataShow full item record
AbstractWe sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmo-dium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at http://totdb.czc.hokudai.ac.jp/. 2012 Hayashida et al. T.
CitationHayashida K, Hara Y, Abe T, Yamasaki C, Toyoda A, et al. (2012) Comparative Genome Analysis of Three Eukaryotic Parasites with Differing Abilities To Transform Leukocytes Reveals Key Mediators of Theileria-Induced Leukocyte Transformation. mBio 3: e00204-12-e00204-12. doi:10.1128/mBio.00204-12.
PublisherAmerican Society for Microbiology
PubMed Central IDPMC3445966
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Divergence of the mitochondrial genome structure in the apicomplexan parasites, Babesia and Theileria.
- Authors: Hikosaka K, Watanabe Y, Tsuji N, Kita K, Kishine H, Arisue N, Palacpac NM, Kawazu S, Sawai H, Horii T, Igarashi I, Tanabe K
- Issue date: 2010 May
- Alteration of host cell phenotype by Theileria annulata and Theileria parva: mining for manipulators in the parasite genomes.
- Authors: Shiels B, Langsley G, Weir W, Pain A, McKellar S, Dobbelaere D
- Issue date: 2006 Jan
- Evolution and diversity of secretome genes in the apicomplexan parasite Theileria annulata.
- Authors: Weir W, Karagenç T, Baird M, Tait A, Shiels BR
- Issue date: 2010 Jan 18
- Genome of the host-cell transforming parasite Theileria annulata compared with T. parva.
- Authors: Pain A, Renauld H, Berriman M, Murphy L, Yeats CA, Weir W, Kerhornou A, Aslett M, Bishop R, Bouchier C, Cochet M, Coulson RM, Cronin A, de Villiers EP, Fraser A, Fosker N, Gardner M, Goble A, Griffiths-Jones S, Harris DE, Katzer F, Larke N, Lord A, Maser P, McKellar S, Mooney P, Morton F, Nene V, O'Neil S, Price C, Quail MA, Rabbinowitsch E, Rawlings ND, Rutter S, Saunders D, Seeger K, Shah T, Squares R, Squares S, Tivey A, Walker AR, Woodward J, Dobbelaere DA, Langsley G, Rajandream MA, McKeever D, Shiels B, Tait A, Barrell B, Hall N
- Issue date: 2005 Jul 1
- Molecular detection and genetic identification of Babesia bigemina, Theileria annulata, Theileria orientalis and Anaplasma marginale in Turkey.
- Authors: Zhou M, Cao S, Sevinc F, Sevinc M, Ceylan O, Moumouni PFA, Jirapattharasate C, Liu M, Wang G, Iguchi A, Vudriko P, Suzuki H, Xuan X
- Issue date: 2016 Feb
Showing items related by title, author, creator and subject.
Cell penetrating peptides to dissect host-pathogen protein-protein interactions in Theileria -transformed leukocytesHaidar, Malak; de Laté, Perle Latré; Kennedy, Eileen J.; Langsley, Gordon (Bioorganic & Medicinal Chemistry, Elsevier BV, 2017-09-08) [Article]One powerful application of cell penetrating peptides is the delivery into cells of molecules that function as specific competitors or inhibitors of protein-protein interactions. Ablating defined protein-protein interactions is a refined way to explore their contribution to a particular cellular phenotype in a given disease context. Cell-penetrating peptides can be synthetically constrained through various chemical modifications that stabilize a given structural fold with the potential to improve competitive binding to specific targets. Theileria-transformed leukocytes display high PKA activity, but PKAis an enzyme that plays key roles in multiple cellular processes; consequently genetic ablation of kinase activity gives rise to a myriad of confounding phenotypes. By contrast, ablation of a specific kinase-substrate interaction has the potential to give more refined information and we illustrate this here by describing how surgically ablating PKA interactions with BAD gives precise information on the type of glycolysis performed by Theileria-transformed leukocytes. In addition, we provide two other examples of how ablating specific protein-protein interactions in Theileria-infected leukocytes leads to precise phenotypes and argue that constrained penetrating peptides have great therapeutic potential to combat infectious diseases in general.
miR-34c-3p regulates PKA activity independent of cAMP via ablation of PRKAR2B in Theileria annulata-infected leukocytes and Plasmodium falciparum-infected erythrocytesHaidar, Malak; Ben Rached, Fathia; Wagner, Matthias; Mourier, Tobias; Rchiad, Zineb; Mfarrej, Sara; Chitnis, Chetan E.; Pain, Arnab; Langsley, Gordon (Cold Spring Harbor Laboratory, 2020-04-12) [Preprint]MicroRNAs (miRNAs) are small non-coding RNAs that can play critical roles in regulating various cellular processes including during many parasitic infections. Here, we report a regulatory role for miR-34c-3p in cAMP-independent regulation of PKA activity in Theileria annulata and Plasmodium falciparum infections of bovine leukocytes and human erythrocytes, respectively. We identified prkar2b (cAMP-dependent protein kinase A type II-beta regulatory subunit), as a novel miR-34c-3p target gene and demonstrated how infection-induced up-regulation of miR-34c-3p in leukocytes repressed PRKAR2B expression to increase PKA activity and promote the virulent disseminating tumour phenotype of T. annulata-transformed macrophages. When human erythrocytes are infected by P. falciparum they accumulate miR-34c-3p that ablates both prkar2b and parasite Pfpkar mRNA. However, erythrocytes lack protein translation machinery so only miR-34c-3p-mediated loss of Pfpkar transcripts results in an increase in PfPKA kinase activity. Inhibition of miR-34c-3p increases Pfpkar expression to reduce PfPKA activity leading to slowing of intra-erythrocyte parasite development and a reduction in invasion of fresh red blood cells. Finally, we demonstrate that miR-34c-3p regulation of prkar2b expression is generalizable, by showing that it can negatively regulate prkar2b expression and PRKAR2B protein levels in human cancer cell lines and that brown adipose tissue displays high levels of miR-34c-3p and corresponding low levels of prkar2b mRNA compared to white adipose tissue. Induction of miR-34c-3p therefore, represents a novel cAMP-independent way of regulating PKA activity in a range of cell types associated with cancer, diabetes and parasitic diseases.
Interaction between transforming Theileria parasites and their host bovine leukocytesTajeri, Shahin; Haidar, Malak; Sakura, Takaya; Langsley, Gordon (Molecular Microbiology, Wiley, 2021-02-09) [Article]Theileria are tick-transmitted parasites that cause often fatal leuko-proliferative diseases in cattle called tropical theileriosis (T. annulata) and East Coast fever (T. parva). However, upon treatment with anti-theilerial drug-transformed leukocytes die of apoptosis indicating that Theileria-induced transformation is reversible making infected leukocytes a powerful example of how intracellular parasites interact with their hosts. Theileria-transformed leukocytes disseminate throughout infected cattle causing a cancer-like disease and here, we discuss how cytokines, noncoding RNAs and oncometabolites can contribute to the transformed phenotype and disease pathology.