Parasites lacking the micronemal protein MIC2 are deficient in surface attachment and host cell egress, but remain virulent in vivo

Wellcome Open Research

article

Simon Gras¹  Allison Jackson¹  Stuart Woods²  Gurman Pall¹  Jamie Whitelaw¹  Jacqueline M. Leung³  Gary E. Ward⁴  Craig W. Roberts²  Markus Meissner¹ 

[1] Wellcome Trust Centre For Molecular Parasitology, Institute of Infection, Immunity & Inflammation, Glasgow Biomedical Research Centre, University of Glasgow;Strathclyde Institute of Pharmacy and Biomedical Sciences;Department of Biology, Indiana University;Department of Microbiology and Molecular Genetics, College of Medicine, University of Vermont

关键词: Toxoplasma;    Microneme;    Gliding motility;    Host cell invasion;    TRAP;    MIC2;    Plasmodium;   

DOI  :  10.12688/wellcomeopenres.11594.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Micronemal proteins of the thrombospondin-related anonymous protein (TRAP) family are believed to play essential roles during gliding motility and host cell invasion by apicomplexan parasites, and currently represent major vaccine candidates againstPlasmodium falciparum, the causative agent of malaria. However, recent evidence suggests that they play multiple and different roles than previously assumed. Here, we analyse a null mutant for MIC2, the TRAP homolog inToxoplasma gondii.Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion andin vivo virulence.Results: We verified the role of MIC2 in efficient surface attachment, but were unable to identify any direct function of MIC2 in sustaining gliding motility or host cell invasion once initiated. Furthermore, we find that deletion ofmic2 causes a slightly delayed infectionin vivo, leading only to mild attenuation of virulence; like with wildtype parasites, inoculation with even low numbers ofmic2 KO parasites causes lethal disease in mice. However, deletion ofmic2 causes delayed host cell egressin vitro, possibly via disrupted signal transduction pathways.Conclusions: We confirm a critical role of MIC2 in parasite attachment to the surface, leading to reduced parasite motility and host cell invasion. However, MIC2 appears to not be critical for gliding motility or host cell invasion, since parasite speed during these processes is unaffected. Furthermore, deletion of MIC2 leads only to slight attenuation of the parasite.

【 授权许可】

CC BY