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A conserved apicomplexan microneme protein contributes to Toxoplasma gondii invasion and virulence.
Huynh, My-Hang; Boulanger, Martin J; Carruthers, Vern B.
Afiliación
  • Huynh MH; Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
  • Boulanger MJ; Department of Biochemistry & Microbiology, University of Victoria, Victoria, British Columbia, Canada.
  • Carruthers VB; Department of Microbiology and Immunology, University of Michigan School of Medicine, Ann Arbor, Michigan, USA vcarruth@umich.edu.
Infect Immun ; 82(10): 4358-68, 2014 Oct.
Article en En | MEDLINE | ID: mdl-25092910
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 the sporozoite protein with an altered thrombospondin repeat (SPATR) 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 T. gondii SPATR (TgSPATR) to T. gondii invasion by genetically ablating it and restoring its expression by genetic complementation. Δspatr parasites were ~50% reduced in invasion 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 Plasmodium falciparum SPATR ortholog (PfSPATR) 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxoplasma / Proteínas Protozoarias / Trombospondinas / Factores de Virulencia Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Toxoplasma / Proteínas Protozoarias / Trombospondinas / Factores de Virulencia Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Infect Immun Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos