monensin and Toxoplasmosis--Animal

Infection with the apicomplexan protozoan parasite T. gondii can cause severe and potentially fatal cerebral and ocular disease, especially in immunocompromised individuals. The anticoccidial ionophore drug monensin has been shown to have anti-Toxoplasma gondii properties. However, the comprehensive molecular mechanisms that underlie the effect of monensin on T. gondii are still largely unknown. We hypothesized that analysis of T. gondii transcriptional changes induced by monensin treatment can reveal new aspects of the mechanism of action of monensin against T. gondii.. Porcine kidney (PK)-15 cells were infected with tachyzoites of T. gondii RH strain. Three hours post-infection, PK-15 cells were treated with 0.1 μM monensin, while control cells were treated with medium only. PK-15 cells containing intracellular tachyzoites were harvested at 6 and 24 h post-treatment, and the transcriptomic profiles of T. gondii-infected PK-15 cells were examined using high-throughput RNA sequencing (RNA-seq). Quantitative real-time PCR was used to verify the expression of 15 differentially expressed genes (DEGs) identified by RNA-seq analysis.. A total of 4868 downregulated genes and three upregulated genes were identified in monensin-treated T. gondii, indicating that most of T. gondii genes were suppressed by monensin. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of T. gondii DEGs showed that T. gondii metabolic and cellular pathways were significantly downregulated. Spliceosome, ribosome, and protein processing in endoplasmic reticulum were the top three most significantly enriched pathways out of the 30 highly enriched pathways detected in T. gondii. This result suggests that monensin, via down-regulation of protein biosynthesis in T. gondii, can limit the parasite growth and proliferation.. Our findings provide a comprehensive insight into T. gondii genes and pathways with altered expression following monensin treatment. These data can be further explored to achieve better understanding of the specific mechanism of action of monensin against T. gondii.

Topics: Animals; Cell Line; Down-Regulation; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Host-Parasite Interactions; Kidney; Monensin; Swine; Toxoplasma; Toxoplasmosis, Animal; Transcriptome; Up-Regulation

Toxoplasma gondii. The experiments were conducted in vitro using 2 methods; cysts produced either in mice or in cell culture were exposed to monensin in vitro, and the infectivity of the parasites was then assessed in vivo or in vitro. The data obtained from these 2 systems of evaluation showed that monensin inhibits the infectivity and the viability of the bradyzoites. Its activity was time and concentration dependent. The first effects were observed at very low drug concentrations (i.e. 0.0001 microg/ml). Immunofluorescence and electron microscopy analysis showed significant cytological alterations of the monensin-treated bradyzoites: they were swollen, had a large number of vacuoles in their cytoplasm and were found lysed at higher concentrations in ionophore.

Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Chlorocebus aethiops; Cysts; Fluorescent Antibody Technique; Mice; Microscopy, Electron; Monensin; Toxoplasma; Toxoplasmosis, Animal; Vero Cells

Topics: Animals; Cattle; Female; Monensin; Pregnancy; Sheep; Sheep Diseases; Toxoplasmosis, Animal; Veterinary Medicine

Topics: Animals; Coccidiosis; Delayed-Action Preparations; Monensin; Sheep; Sheep Diseases; Toxoplasmosis, Animal

Topics: Animals; Coccidiosis; Decoquinate; Hydroxyquinolines; Monensin; Sheep; Sheep Diseases; Toxoplasmosis, Animal

Topics: Animals; Monensin; Sheep; Sheep Diseases; Toxoplasmosis, Animal

Topics: Abortion, Veterinary; Animal Feed; Animals; Female; Monensin; Pregnancy; Sheep; Sheep Diseases; Toxoplasmosis, Animal

Monensin was fed to 69 pregnant ewes from 81 to 84 days gestation until lambing, at an estimated rate of nil, 16.8 or 27.9 mg per head per day. Ten days after the start of this regime, groups of the ewes were dosed orally with nil, 2000 or 12,000 sporulated Toxoplasma gondii oocysts. Twenty ewes given T. gondii alone (T ewes) produced 29 lambs or aborted foetuses, 16 (55.2 per cent) of which were born dead. The 39 ewes given monensin and T. gondii (M + T ewes) produced 48 lambs or aborted foetuses, 8 (16.7 per cent) of which were born dead. The 10 ewes given monensin alone produced 12 live lambs. No difference of effect was apparent between the two doses of monensin given, nor between the two doses of Toxoplasma oocysts used. Monensin alone caused no discernible problems. Not only were proportionately more live lambs born to M + T ewes than to T ewes, but they were also heavier, possibly due to a lesser "weight" of infection within the gravid uterus. We conclude that monensin fed at about 16 mg per head per day to pregnant ewes can significantly reduce losses at lambing time due to experimentally administered T. gondii.

Topics: Administration, Oral; Animals; Female; Monensin; Pregnancy; Sheep; Toxoplasma; Toxoplasmosis, Animal; Uterine Diseases

Topics: Animals; Birth Weight; Female; Fetal Death; Gestational Age; Humans; Infant, Newborn; Monensin; Placenta; Pregnancy; Pregnancy Complications, Infectious; Sheep; Sheep Diseases; Toxoplasmosis, Animal

Development of immunity to the shedding of oocysts was examined in 75 kittens that survived infection with the three stages of Toxoplasma gondii. Of 16 kittens fed bradyzoites in cysts, 94% were immune and did not shed oocysts. Of seven injected with tachyzoites 86% were immune. Of 18 fed sporozoites only 11% were immune, but following injection, 54% of 12 were immune. After the administration of either bradyzoites or tachyzoites from nonoocyst-producing strains, only 9% of 22 were immune. Considering all inocula, immunity was present in 93% of kittens that had previously shed oocysts, 25% of those that only develop antibody, and none that had neither shed nor developed an antibody titer. After a second challenge with a different isolate, a similar percentage of immunity was observed. Infection with killed tachyzoites, alone, or together with Freund's complete or incomplete adjuvants was followed by immunity in only one of 24 kittens. Eighty-five percent of 13 kittens were immune, after they had been treated prophylactically with 200 mg/kg monensin, or 60 mg/kg cat sulfadiazine combined with 1 mg/kg cat of pyrimethamine; oocyst shedding had been suppressed in all. It is concluded that cats can be immunized against oocyst shedding by infections where oocysts are produced, or where developmental stages are suppressed by chemoprophylaxis, but not if enteroepithelial stages are absent, as in the oocyst-less strain examined.

Topics: Animals; Antibodies; Cat Diseases; Cats; Feces; Immunization; Mice; Monensin; Parasite Egg Count; Pyrimethamine; Sulfadiazine; Toxoplasma; Toxoplasmosis, Animal

Toxoplasma oocyst shedding by cats was suppressed by 0.02% monensin incorporated in dry cat food. Ten of 12 cats that had not shed oocysts were immune when reinfected with mice chronically infected with Toxoplasma. The medicated food, which was well accepted and tolerated by kittens, could be useful to minimize risks of infection for pregnant women and small children from pet cats defecating in soil close to homes. However, in the presence of stray cats a false sense of security may be engendered.

Topics: Animals; Cat Diseases; Cats; Feces; Female; Furans; Mice; Monensin; Parasite Egg Count; Toxoplasmosis, Animal