Article
Toxoplasma gondii proteomics.
Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Forchheimer 504, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Expert Review of Proteomics (impact factor:
3.68).
07/2009;
6(3):303-13.
DOI:10.1586/epr.09.16
pp.303-13
Source: PubMed
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Article: Proteolysis and Toxoplasma invasion.
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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 -
Article: Rhoptries: an arsenal of secreted virulence factors.
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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.
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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
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Keywords
Apicomplexan parasite
applicable experimental techniques available
clinical syndromes
Ctenodoactylus gundi
current status
elucidate specialized invasion organelles
EPIC-DB
genome annotation
Global proteomic studies
improved understanding
intracellular pathogens
model organism
protein regulation
proteomic data
proteomic studies
subcellular proteomic studies
T. gondii
Toxoplasma gondii
type II
type III
