Infect Immun. 2009 Jul 6. [Epub ahead of print]
Transmembrane domain containing surface protein from Toxoplasma gondii augments replication in activated immune cells and the establishment of a chronic infection
Pollard AM, Skariah S, Mordue DG, Knoll LJ.
Toxoplasma gondii mutants identified as defective in the establishment of chronic infection were screened to isolate those specifically impaired in their ability to replicate within activated macrophages. One of the identified mutants contains an insertion in hypothetical gene TGME49_111670. Genetic complementation restores the ability of the mutant to replicate in immune cells and produce cysts in the brains of mice. While the mutant is more sensitive to nitric oxide compared to its parental strain, it is not defective in its ability to suppress nitric oxide. The disrupted protein has no significant homology to proteins with known functions, but is predicted to have one transmembrane domain. Immunofluorescence shows the protein on the parasite surface even in activated macrophages, co-localizing with a tachyzoite surface antigen SAG1, and oriented with its C-terminal end external. Western analysis reveals that the protein is down regulated in bradyzoites. Despite the tachyzoite-specificity of this protein, mice infected with the mutant succumb to acute infection similarly to those infected with the parent strain. Serum from mice with a chronic T. gondii infection reacts to a polypeptide from TGME49_11670, indicating that the protein is seen by the immune system during infection. This study is the first to characterize a T. gondii surface protein that contains a transmembrane domain, and show that the protein contributes to parasite replication in activated immune cells and the establishment of chronic infection.
PMID: 19581395 [PubMed - as supplied by publisher]