Murillo-Leon, Mateo, Mueller, Urs B., Zimmermann, Ines, Singh, Shishir ORCID: 0000-0002-8488-3992, Widdershooven, Pia, Campos, Claudia ORCID: 0000-0003-1809-8272, Alvarez, Catalina, Koenen-Waisman, Stephanie, Lukes, Nahleen, Ruzsics, Zsolt, Howard, Jonathan C., Schwemmle, Martin and Steinfeldt, Tobias (2019). Molecular mechanism for the control of virulent Toxoplasma gondii infections in wild-derived mice. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1(CIM) to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1(CIM), indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Murillo-Leon, MateoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Urs B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zimmermann, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singh, ShishirUNSPECIFIEDorcid.org/0000-0002-8488-3992UNSPECIFIED
Widdershooven, PiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Campos, ClaudiaUNSPECIFIEDorcid.org/0000-0003-1809-8272UNSPECIFIED
Alvarez, CatalinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenen-Waisman, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lukes, NahleenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruzsics, ZsoltUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Howard, Jonathan C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwemmle, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinfeldt, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-153728
DOI: 10.1038/s41467-019-09200-2
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMMUNITY-RELATED GTPASES; IRG RESISTANCE GTPASES; PSEUDOKINASE ROP5; GENETIC DIVERSITY; CELLULAR-RESPONSE; HOST-RESISTANCE; FAMILY; STRAINS; MOUSE; SUPERFAMILYMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15372

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