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

Gras, S., Jackson, A., Woods, S., Pall, G., Whitelaw, J., Leung, J. M., Ward, G. E., Roberts, C. W. and Meissner, M. (2017) Parasites lacking the micronemal protein MIC2 are deficient in surface attachment and host cell egress, but remain virulent in vivo. Wellcome Open Research, 2, 32. (doi:10.12688/wellcomeopenres.11594.1) (PMID:28630943) (PMCID:PMC5473411)

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Abstract

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 against Plasmodium 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 in Toxoplasma gondii. Methods: We performed a careful analysis of parasite motility in a 3D-environment, attachment under shear stress conditions, host cell invasion and in 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 of mic2 causes a slightly delayed infection in vivo, leading only to mild attenuation of virulence; like with wildtype parasites, inoculation with even low numbers of mic2 KO parasites causes lethal disease in mice. However, deletion of mic2 causes delayed host cell egress in 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.

Item Type:Articles
Additional Information:Version 1; referees: 1 approved, 2 approved with reservations.
Keywords:Gliding motility, host cell invasion, MIC2, microneme, plasmodium, TRAP, toxoplasma.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Whitelaw, Mr Jamie and Gras, Dr Simon and Meissner, Professor Markus and Ward, Professor Gary and Pall, Dr Gurman and Jackson, Dr Allison
Authors: Gras, S., Jackson, A., Woods, S., Pall, G., Whitelaw, J., Leung, J. M., Ward, G. E., Roberts, C. W., and Meissner, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Wellcome Open Research
Publisher:F1000Research
ISSN:2398-502X
ISSN (Online):2398-502X
Copyright Holders:Copyright © 2017 Gras S et al.
First Published:First published in Wellcome Open Research 2: 32
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
501601Systematic analysis of essential parasite genes linked to invasion of the host cell in Toxoplasma gondiiMarkus MeissnerWellcome Trust (WELLCOTR)087582/Z/08/ZIII - PARASITOLOGY
653211Essential or redundant: Dissection of apicomplexan invasion mechanismsMarkus MeissnerWellcome Trust (WELLCOTR)103875/Z/14/ZIII - PARASITOLOGY
371796The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)085349/Z/08/ZIII - PARASITOLOGY