Wednesday, August 06, 2014

A conserved apicomplexan microneme protein contributes to T. gondii invasion and virulence

 2014 Aug 4. pii: IAI.01877-14. [Epub ahead of print]

Abstract

The obligate intracellular parasite Toxoplasma gondii critically relies on host cell invasion during infection. Proteins secreted from the apical micronemes are central components for host cell recognition, invasion, egress and virulence. Although previous work established that SPATR (Sporozoite Protein with an Altered Thrombospondin Repeat) is a micronemal protein conserved in other apicomplexan parasites including Plasmodium, Neospora and Eimeria, no genetic evidence of its contribution to invasion has been reported. SPATR contains a predicted epidermal growth factor domain and two thrombospondin type 1 repeats, implying a role in host cell recognition. In this study we assess the contribution of TgSPATR to T. gondii invasion by genetically ablating it and restoring its expression by genetic complementation. Δspatr parasites were ∼50% reduced in invasion when compared to parental strains, a defect that was reversed in the complemented strain. In mouse virulence assays, Δspatr parasites were significantly attenuated, with ∼20% of mice surviving infection. Given the conservation of this protein among the Apicomplexa, we assessed whether the P. falciparum ortholog could complement the absence of the TgSPATR. Although PfSPATR showed correct micronemal localization, it did not reverse the invasion deficiency of Δspatr parasites because of an apparent failure in secretion. Overall the results suggest that TgSPATR contributes to invasion and virulence, findings that have implications for the many genera and life stages of apicomplexans that express SPATR.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PMID:
 
25092910
 
[PubMed - as supplied by publisher]

No comments: