Tazonomy of Toxoplasma.

After reviewing reports of the hosts, structure and life cycle of Toxoplasma, the genus is placed in the apicomplexan family Eimeriidae and the folllowing 7 species are recognized: Toxoplasma gondii (Nicolle & Manceaux) (type species) from about 200 species of mammals and birds, with oocysts in felids; Toxoplasma alencari (Da Costa & Pereira) from the frog Leptodactylus ocellatus; Toxoplasma brumpti Coutelen from the iguana Iguana tuberculata; Toxoplasma colubri Tibaldi from the snakes Coluber melanoleucus and Coluber viridiflavus; Toxoplasma hammondi (Frenkel & Dubey) (a new combination for Hammondia hammondi) from the house mouse with oocysts in the domestic cat; Toxoplasma ranae Levine & Nye from the leopard frog Rana Pipiens; and Toxoplasma serpai Scorza, Dagert & Iturriza Arocha from the toad Bufo marinus.     

Toxoplasma gondii: characterization of a mutant resistant to sulfonamides.

Sulfadiazine was a potent inhibitor of the in vitro growth of Toxoplasma gondii, although it had little effect during the first 24 hr of treatment. A mutant parasite (R-SulR-5) with a 300-fold increase in sulfadiazine resistance was selected by a combination of chemical mutagenesis and growth in gradually increased sulfadiazine concentrations. This mutant was completely cross-resistant to several other sulfonamides and to dapsone. The same concentration of p-aminobenzoic acid reversed the sulfadiazine inhibition of both mutant and wild-type parasites even though much higher concentrations of sulfadiazine were used to inhibit the mutant. Dihydropteroate synthase, a sulfonamide-sensitive enzyme in the pathway leading to dihydrofolic acid, had similar activities in wild-type and R-SulR-5 parasites. However, the mutant enzyme was 40-fold more resistant to sulfadiazine and had higher apparent Kms for both substrates, p-aminobenzoic acid and dihydropteridine pyrophosphate. The mutant was slightly less active than the wild type in the uptake of sulfadiazine.     

Toxoplasma gondii micronemal protein MIC1 is a lactose-binding lectin.

Host cell invasion by Toxoplasma gondii is a multistep process with one of the first steps being the apical release of micronemal proteins that interact with host receptors. We demonstrate here that micronemal protein 1 (MIC1) is a lactose-binding lectin. MIC1 and MIC4 were recovered in the lactose-eluted (Lac(+)) fraction on affinity chromatography on immobilized lactose of the soluble antigen fraction from tachyzoites of the virulent RH strain. MIC1 and MIC4 were both identified by N-terminal microsequencing. MIC4 was also identified by sequencing cDNA clones isolated from an expression library following screening with mouse polyclonal anti-60/70 kDa (Lac(+) proteins) serum. This antiserum localized the Lac(+) proteins on the apical region of T. gondii tachyzoites by confocal microscopy. The Lac(+) fraction induced hemagglutination (mainly type A human erythrocytes), which was inhibited by beta-galactosides (3 mM lactose and 12 mM galactose) but not by up to 100 mM melibiose (alpha-galactoside), fucose, mannose, or glucose or 0.2 mg/ml heparin. The lectin activity of the Lac(+) preparation was attributed to MIC1, because blotted MIC1, but not native MIC4, bound human erythrocyte type A and fetuin. The copurification of MIC1 and MIC4 may have been due to their association, as reported by others. These data suggest that MIC1 may act through its lectin activity during T. gondii infection.     

Toxoplasma antibodies in ophthalmological patients.

Sera of 532 patients suffering from different ophthalmological diseases were studied for the presence of toxoplasma antibodies. Complement fixation test was positive in 44.9% of the patients. As compared with the 26.8% positivity rate determined earlier in the normal population the seropositivity in eye-patients was significantly higher. The highest incidence, 50%, was found in the age group of 21--30 years. In diseases with a confirmed aetiological role of toxoplasmosis, the incidence of seropositivity was higher than in the total material. This suggests that Toxoplasma gondii may have had a role in part of the diseases of the patients studied.     

Isolation of Toxoplasma gondii from a naturally infected beef cow.

Toxoplasma gondii was isolated from the intestinal wall of an adult shorthorn cow. The cow had an antibody titer of 1:1,600 in the T. gondii agglutination test using formalin-fixed whole tachyzoites. The strain of the parasite designated CT-1 was lethal to mice. This is the first report of the recovery of viable T. gondii from a naturally infected cow in the United States.     

Lytic cycle of Toxoplasma gondii.

Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. This protozoan parasite is one of the most widespread, with a broad host range including many birds and mammals and a geographic range that is nearly worldwide. While infection of healthy adults is usually relatively mild, serious disease can result in utero or when the host is immunocompromised. This sophisticated eukaryote has many specialized features that make it well suited to its intracellular lifestyle. In this review, we describe the current knowledge of how the asexual tachyzoite stage of Toxoplasma attaches to, invades, replicates in, and exits the host cell. Since this process is closely analogous to the way in which viruses reproduce, we refer to it as the Toxoplasma "lytic cycle."     

Review: Toxoplasma gondii cellular invasion.

Toxoplasma gondii, the etiologic agent of toxoplasmosis, is a ubiquitous protozoan parasite that requires an intracellular site for growth and replication. The invasive process involves six steps: a) cellular recognition, b) parasite movements by means of a subpellicular microtubule cytoskeleton, c) cell to cell adhesion, d) rhoptry secretion of penetrating enhancing factor (PEF) with Ca++ and Ca++ activated ATPase dependence, e) conoid penetration, f) induction of a parasitophorous vacuole, a protective and exchange site, interiorization of the parasite. The invasion is an active, oriented and specific process depending on chemical factors as energy sources, cations, as well as microviscosity and membrane structures. Toxoplasma gondii stimulates T cell subsets and induces lymphokine (IFN gamma, IL2) release.     

Toxoplasma gondii infection and schizophrenia: a case control study in a low Toxoplasma seroprevalence Mexican population

There are conflicting reports concerning the association of Toxoplasma gondii infection and schizophrenia in humans. Therefore, we determined such association in a Mexican population of Mestizo ethnicity. Through a case-control study design, 50 schizophrenic patients and 150 control subjects matched by gender, age, residence place, and ethnicity were examined with enzyme-linked immunoassays for the presence and levels of T. gondii IgG antibodies and for the presence of T. gondii IgM antibodies. Schizophrenic patients attended a public psychiatric hospital in Durango City, Mexico, and the control group consisted of individuals of the general population of the same city. Socio-demographic, clinical and behavioral characteristics from the study subjects were also obtained. Both the seroprevalence and the level of T.gondii IgG antibodies were higher in schizophrenic patients (10/50; 20%) than in control subjects (8/150; 5.3%) (OR=4.44; 95% CI: 1.49-13.37; P=0.003). The IgG T. gondii levels higher than 150 IU/ml were more frequently observed in patients than in controls (10% versus 2%, respectively; P=0.02). One (50%) of the two patients with recently diagnosed schizophrenia and none of the controls had T. gondii IgM antibodies (P=0.01). T. gondii seropositivity was significantly higher in patients with a history of cleaning cat excrement (P=0.005), and suffering from simple schizophrenia (ICD-10 classification: F20.6) (P=0.03) than patients without these characteristics. Toxoplasma seroprevalence was also significantly higher in patients with simple schizophrenia (F20.6) than in those with paranoid schizophrenia (F20.0) (P=0.02). This study provides elements to clarify the controversial information on the association of T. gondii infection and schizophrenia.     

Immunization of NMRI mice against virulent Toxoplasma gondii. Differing efficacy of eleven cyst-forming Toxoplasma strains

Mice were infected with eleven cyst-forming Toxoplasma strains of varying virulence and challenged 1 month later with highly virulent BK strain parasites. The early cellular reaction in vivo was estimated by collecting the peritoneal exudates 24 h after challenge. This consisted of 54.34--77.61% lymphocytes and 0-8.88% infected macrophages in the eleven immunized groups in contrast to 27.17% lymphocytes and 18.64% infected macrophages in the control group. The peritoneal exudate 72 h after challenge comprised of 55.88-73.86% lymphocytes and 0-6.97% infected macrophages compared to 25.88% lymphocytes and 92% infected macrophages in the control group. Following the virulent challenge, deaths occurred in seven of the eleven groups immunized with live strains and ranged 5-42% at the end of a 6-week observation period. The most virulent of the Toxoplasma strains used - Alt and Gail - gave higher mortality while the least virulent ones - 558, 1070, K8 and KSU - were solidly resistant. The significantly different mortality obtained with strains Alt, Gail and Witting in a similar experiment performed at an interval of 7 months is discussed.     

Toxoplasma as a novel system for motility

Motility is a characteristic of most living organisms and often requires specialized structures like cilia or flagella. An alternative is amoeboid movement, where the polymerization/depolymerization of actin leads to the formation of pseudopodia, filopodia and/or lamellipodia that enable the cell to crawl along a surface. Despite their lack of locomotive organelles and in absence of cell deformation, members of the apicomplexan parasites employ a unique form of locomotion called gliding motility to promote their migration across biological barriers and to power host-cell invasion and egress. Detailed studies in Toxoplasma gondii and Plasmodium species have revealed that this unique mode of movement is dependent on a myosin of class XIV and necessitates actin dynamics and the concerted discharge and processing of adhesive proteins. Gliding is essential for the survival and infectivity of these obligate intracellular parasites, which cause severe disease in humans and animals.