Toxoplasma gondii proteomics.
ABSTRACT Toxoplasma gondii is a ubiquitous, Apicomplexan parasite that, in humans, can cause several clinical syndromes, including encephalitis, chorioretinitis and congenital infection. T. gondii was described a little over 100 years ago in the tissues of the gundi (Ctenodoactylus gundi). There are a large number of applicable experimental techniques available for this pathogen and it has become a model organism for the study of intracellular pathogens. With the completion of the genomes for a type I (GT-1), type II (ME49) and type III (VEG) strains, proteomic studies on this organism have been greatly facilitated. Several subcellular proteomic studies have been completed on this pathogen. These studies have helped elucidate specialized invasion organelles and their composition, as well as proteins associated with the cytoskeleton. Global proteomic studies are leading to improved strategies for genome annotation in this organism and an improved understanding of protein regulation in this pathogen. Web-based resources, such as EPIC-DB and ToxoDB, provide proteomic data and support for studies on T. gondii. This review will summarize the current status of proteomic research on T. gondii.
Article: Proteolysis and Toxoplasma invasion.[show abstract] [hide abstract]
ABSTRACT: Apicomplexan parasites including Toxoplasma gondii cause widespread human and animal diseases, often with the most severe manifestations involving the central nervous system. The need for new therapeutic agents along with the fascinating biology of these parasites has fueled a keen interest in understanding how key steps in the life cycle are regulated. Proteolysis is intimately associated with cell and tissue invasion by these obligate intracellular parasites and recent studies have begun to identify the proteases involved in these processes. Based on clues from inhibitor experiments and cleavage site mapping studies, several groups are using emerging genome information, chemical proteomics and molecular genetics to identify and validate proteases that regulate secretory organelle biogenesis and invasion protein activity. These studies are revealing roles for an assortment of proteases including cathepsins, subtilases and rhomboids in cell and tissue invasion. The identification of highly selective inhibitors for these proteases has the potential to not only further dissect their roles in infection but also to ameliorate disease.International Journal for Parasitology 06/2006; 36(5):595-600. · 3.39 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Apicomplexan parasites use actin-based motility coupled with regulated protein secretion from apical organelles to actively invade host cells. Crucial in this process are rhoptries, club-shaped secretory organelles that discharge their contents during parasite invasion into host cells. A proteomic analysis of the rhoptries in Toxoplasma gondii demonstrated that this organelle contains a number of novel rhoptry proteins (ROPs) including serine-threonine kinases and protein phosphatases. A subset of rhoptry proteins called RONs have been shown to target the moving junction, which plays a key role in invasion and parasitophorous vacuole formation. Other ROP proteins have various destinations in the host cell including the host cell nucleus and the parasitophorous vacuole, probably reflecting their distinct targets and roles. Forward genetic analysis recently revealed that secretory ROP kinases dramatically influence host gene expression and are the major parasite virulence factors. Thus, ROP proteins are functionally analogous (though not homologous) to effectors released by type III and IV secretion systems, which are factors that play an important role in bacterial virulence. Deciphering the role of ROP effectors may allow specific disruption of these factors, thus offering new options for preventing disease.Current Opinion in Microbiology 01/2008; 10(6):582-7. · 7.93 Impact Factor
Article: Outbreak of toxoplasmosis associated with municipal drinking water. The BC Toxoplasma Investigation Team.[show abstract] [hide abstract]
ABSTRACT: Outbreaks of toxoplasmosis are recognised infrequently. In March, 1995, a sudden increase of serologically diagnosed cases of acute toxoplasmosis was noted in the Greater Victoria area of British Columbia, Canada. Concurrently, but independently, seven cases of acute toxoplasma retinitis were diagnosed against a background of no cases in the previous 5 years. Cases were defined by serological testing, clinical presentation, and residence in Greater Victoria. A screening programme for women who were or had been pregnant was started. Geographical mapping of cases, and case-control studies of symptomatic cases and of women enrolled in the screening programme were done. 100 individuals aged 6 to 83 years met the definition for an acute, outbreak-related case. 94 resided in Greater Victoria and six had visited it; 19 had retinitis, 51 had lymphadenopathy, four others had symptoms consistent with toxoplasmosis, seven had other symptoms, 18 were symptom-free, and one would not provide information. 36 (0.9%) of 3812 screened pregnant and postnatal women were cases. Excess cases were not detected outside Greater Victoria and no conventional source of toxoplasmosis was implicated. Mapping studies of cases and of the screened women, and both case-control studies showed significant associations between acute infection and residence in the distribution system of one reservoir supplying water to Greater Victoria (ORs or RRs: 3.53, 3.05, 8.27, and 5.42, respectively). The epidemic curve appeared bimodal, with peaks in December, 1994, and March, 1995, that were preceded by increased rainfall and turbidity in the implicated reservoir. A municipal water system that uses unfiltered, chloraminated surface water was the likely source of this large community-wide outbreak of toxoplasmosis.The Lancet 08/1997; 350(9072):173-7. · 38.28 Impact Factor