Evaluation of the Effect of Drugs on the Cyst Form of Toxoplasma gondii

Huskinson-Mark, J.; Araujo, Fausto G.; Remington, Jack S.

doi:10.1093/infdis/164.1.170

Cited by 159 publications

(69 citation statements)

References 15 publications

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“…with either 10 cysts of the Me49 strain of T. gondii (kindly provided by L. L. Johnson, Saranac Lake, N.Y.) or 10 cysts of N. caninum (kindly provided by J. D. Barta, University of Guelph, Guelph, Ontario, Canada). Cysts were obtained from isolated brain homogenates of infected mice, purified by Percoll centrifugation (25), and diluted in phosphate-buffered saline. Control mice were injected with 0.5 ml of phosphate-buffered saline.…”

Section: Methodsmentioning

confidence: 99%

Responses of Adipose and Muscle Lipoprotein Lipase to Chronic Infection and Subsequent Acute Lipopolysaccharide Challenge

Picard

Arsenijevic

Richard

et al. 2002

Clin Vaccine Immunol

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Infection of male Swiss Webster mice with Toxoplasma gondii or Neospora caninum leads to long-term alterations in energy balance. Following an initial 20 to 30% weight loss in all T. gondii-infected mice, half of the animals regain most of the lost weight (gainers), whereas the others maintain their low body weight (nongainers). Infection with N. caninum does not elicit weight loss. Lipoprotein lipase (LPL), the enzyme responsible for plasma triglyceride (TG) clearance and partitioning among tissues, is under tissue-specific modulation associated with energy balance. It is also a major determinant of infection-induced hypertriglyceridemia. This study aimed to assess the long-term modulation of adipose and muscle LPL activity in mice infected with T. gondii or N. caninum, to evaluate the effects of subsequent acute lipopolysaccharide (LPS) administration, and to relate LPL modulation in these conditions with infection-related changes in body weight gain. Twenty-eight days after infection, LPL activity in muscle of both gainer and nongainer T. gondii-infected mice was reduced by 40 to 50% compared with the levels in controls and N. caninum-infected mice, whereas LPL activity in adipose depots remained unchanged in all infected groups compared to the level in controls. LPS (from Escherichia coli, 100 ng/kg) injection induced a global reduction in adipose LPL in all groups, as assessed 90 min later. In both T. gondii-infected subgroups, muscle LPL was not further reduced by LPS treatment, whereas it was decreased by 40 to 50% in muscles of control and N. caninum-infected mice. Pre-LPS TG levels in plasma were similar in all groups. LPS greatly increased TG levels in plasma in both control and N. caninum-infected animals, whereas it did not alter those of T. gondii-infected gainer or nongainer animals. These results show that (i) independently of the extent of postinfection weight gain, long-term infection with T. gondii chronically reduces muscle LPL, which becomes unresponsive to acute endotoxemia; (ii) modulation of tissue LPL activity during chronic T. gondii infection favors TG partitioning towards adipose tissue; and (iii) skeletal muscle LPL is a key determinant of the acute response of triglyceridemia to LPS.

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Section: Methodsmentioning

confidence: 99%

Responses of Adipose and Muscle Lipoprotein Lipase to Chronic Infection and Subsequent Acute Lipopolysaccharide Challenge

Picard

Arsenijevic

Richard

et al. 2002

Clin Vaccine Immunol

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“…The method used to purify bradyzoite cysts from mouse brains was modified from a previously described protocol (27). Briefly, the brain was passed through a 100-m cell strainer as described above, washed once in 3% FBS/PBS, and brought up to 9 ml in 3% FBS/PBS.…”

Section: Methodsmentioning

confidence: 99%

Bradyzoite Pseudokinase 1 Is Crucial for Efficient Oral Infectivity of the Toxoplasma gondii Tissue Cyst

2013

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The tissue cyst formed by the bradyzoite stage of Toxoplasma gondii is essential for persistent infection of the host and oral transmission. Bradyzoite pseudokinase 1 (BPK1) is a component of the cyst wall, but nothing has previously been known about its function. Here, we show that immunoprecipitation of BPK1 from in vitro bradyzoite cultures, 4 days postinfection, identifies at least four associating proteins: MAG1, MCP4, GRA8, and GRA9. To determine the role of BPK1, a strain of Toxoplasma was generated with the bpk1 locus deleted. This BPK1 knockout strain (⌬bpk1) was investigated in vitro and in vivo. No defect was found in terms of in vitro cyst formation and no difference in pathogenesis or cyst burden 4 weeks postinfection (wpi) was detected after intraperitoneal (i.p.) infection with ⌬bpk1 tachyzoites, although the ⌬bpk1 cysts were significantly smaller than parental or BPK1-complemented strains at 8 wpi. Pepsin-acid treatment of 4 wpi in vivo cysts revealed that ⌬bpk1 parasites are significantly more sensitive to this treatment than the parental and complemented strains. Consistent with this, 4 wpi ⌬bpk1 cysts showed reduced ability to cause oral infection compared to the parental and complemented strains. Together, these data reveal that BPK1 plays a crucial role in the in vivo development and infectivity of Toxoplasma cysts.

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“…Clarithromycin (lot 134-974-AX; Abbott Laboratories, Abbott Park, Ill.) was dissolved in phosphate-buffered saline (PBS; pH 6.8), sonicated before each administration, and given orally through a feeding needle. Minocycline HCI (lot 798; Lederle Laboratories, Division of American Cyanamid Co.) was dissolved in distilled water, the desired concentrations were prepared in polyethylene glycol 500 as previously described (6) (2); cysts were collected from brains of chronically infected mice (12).…”

Section: Methodsmentioning

confidence: 99%

Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis

Araujo

Prokocimer

Lin

et al. 1992

Antimicrob Agents Chemother

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The activity of the macrolide antibiotic clarithromycin was examined alone or in combination with other drugs for the treatment of acute or chronic infections with Toxoplasma gondii in mice. A dose of 300 mg of clarithromycin per kg per day administered alone for 10 days, beginning 24 hours after infection, protected 10 to 30% of mice infected with lethal inocula of tachyzoites or tissue cysts of different strains of T. gondii, including some strains isolated from patients with both AIDS and toxoplasmosis. Although clarithromycin was protective, a wide variation in its activity against different strains was observed. Survival of infected mice was increased significantly by treatment with clarithromycin in combination with pyrimethamine or with sulfadiazine. Treatment of chronically infected mice with clarithromycin at 300 mg/kg/day administered alone for 8 weeks resulted in significant reduction in the numbers of T. gondii cysts in their brains. The combination of clarithromycin and minocycline resulted in an activity against T. gondii cysts that was significantly greater than the activity of clarithromycin or minocycline administered alone. These results indicate a role for clarithromycin in the treatment of human toxoplasmosis, particularly when this antibiotic is used in combination with other drugs with activity against T. gondii.

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Evaluation of the Effect of Drugs on the Cyst Form of Toxoplasma gondii

Cited by 159 publications

References 15 publications

Responses of Adipose and Muscle Lipoprotein Lipase to Chronic Infection and Subsequent Acute Lipopolysaccharide Challenge

Responses of Adipose and Muscle Lipoprotein Lipase to Chronic Infection and Subsequent Acute Lipopolysaccharide Challenge

Bradyzoite Pseudokinase 1 Is Crucial for Efficient Oral Infectivity of the Toxoplasma gondii Tissue Cyst

Activity of clarithromycin alone or in combination with other drugs for treatment of murine toxoplasmosis

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