Synergistic role of micronemal proteins in Toxoplasma gondii virulence

Abstract

Apicomplexan parasites invade cells by a unique mechanism involving discharge of secretory vesicles called micronemes. Microneme proteins (MICs) include transmembrane and soluble proteins expressing different adhesive domains. Although the transmembrane protein TRAP and its homologues are thought to bridge cell surface receptors and the parasite submembranous motor, little is known about the function of other MICs. We have addressed the role of MIC1 and MIC3, two soluble adhesins of Toxoplasma gondii, in invasion and virulence. Single deletion of the MIC1 gene decreased invasion in fibroblasts, whereas MIC3 deletion had no effect either alone or in the mic1KO context. Individual disruption of MIC1 or MIC3 genes slightly reduced virulence in the mouse, whereas doubly depleted parasites were severely impaired in virulence and conferred protection against subsequent challenge. Single substitution of two critical amino acids in the chitin binding–like (CBL) domain of MIC3 abolished MIC3 binding to cells and generated the attenuated virulence phenotype. Our findings identify the CBL domain of MIC3 as a key player in toxoplasmosis and reveal the synergistic role of MICs in virulence, supporting the idea that parasites have evolved multiple ligand–receptor interactions to ensure invasion of different cells types during the course of infection.

A new thrombospondin-related anonymous protein homologue in Neospora caninum (NcMIC2-like1)

“…function for attachment and initiation of invading processes (Soldati et al 2001;Cérède et al 2005;Ravindran and Boothroyd, 2008). Here we have demonstrated that NcMIC2-like1 is mainly located in the apical region of the tachyzoite, possibly in the micronemes, such as demonstrated for NcMIC2 (Lovett et al 2000), TgMIC2 , TgMIC 3 (El-Hajj et al 2008) and NcAMA 1 (Zhang et al 2006).…”

Toxoplasmosis in HIV/AIDS Patients - A Living Legacy

“…T. gondii excretory/secretory antigens (ESAs) are an excellent serological marker for the diagnosis of CT in AIDS patients (Pereira-Chioccola et al, 2009). ESAs are produced by T. gondii tachyzoites, the form responsible for disease dissemination, which plays an important role in stimulating humoral and cellular immunities in order to control Toxoplasma infection (Carruthers & Sibley, 1997;Cérède et al, 2005). Anti-ESA IgG antibodies are also present in C S F s a m p l e o f A I D S p a t i e n t s w i t h C T w h i c h c a n b e d e t e r m i n e d b y E S A -E L I S A a n d immunoblot techniques and these samples are clearly distinguishable from AIDS patients who are Toxoplasma seropositive but with other brain diseases (Pereira-Chioccola et al, 2009).…”

Diversity of extracellular proteins during the transition from the ‘proto-apicomplexan’ alveolates to the apicomplexan obligate parasites

“…2A; Friedrich et al 2010); and recognition of host carbohydrates mediated by an N-terminal domain within the microneme-secreted proteins MIC3 and MIC8 (CBL domain shown in TGME49_286740, Fig. 2A) during host cell invasion by Toxoplasma tachyzoites (Céréde et al 2005). These carbohydrate-binding domains appear to be specific to 1 or more apicomplexan genera and are not found in proto-apicomplexans.…”