Development of a murine vertical transmission model for Toxoplasma gondii oocyst infection and studies on the efficacy of bumped kinase inhibitor (BKI)-1294 and the naphthoquinone buparvaquone against congenital toxoplasmosis
| Autor: | Luis Miguel Ortega-Mora, Matthew A. Hulverson, Andrew Hemphill, Dustin J. Maly, Ignacio Ferre, Wes Van Voorhis, Kayode K. Ojo, Molly C. McCloskey, Ryan Choi, Joachim Müller, Adriana Aguado-Martínez, Lynn K. Barrett, Javier Moreno-Gonzalo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Microbiology (medical) Transplacental transmission medicine.medical_treatment 030106 microbiology Antiprotozoal Agents Naphthalenes Immunofluorescence Toxoplasmosis Congenital Mice 03 medical and health sciences Piperidines 540 Chemistry parasitic diseases medicine Animals Pharmacology (medical) Seroconversion Original Research Pharmacology Chemotherapy Pregnancy 630 Agriculture medicine.diagnostic_test biology business.industry Toxoplasma gondii biology.organism_classification medicine.disease Virology Infectious Disease Transmission Vertical Toxoplasmosis 3. Good health Disease Models Animal Toxoplasmosis Animal Treatment Outcome 030104 developmental biology Infectious Diseases 570 Life sciences Pyrazoles Female business Buparvaquone Naphthoquinones medicine.drug |
| Zdroj: | Müller, Joachim; Aguado Martinez, Adriana; Ortega-Mora, Luis-Miguel; Moreno-Gonzalo, Javier; Ferre, Ignacio; Hulverson, Matthew A; Choi, Ryan; McCloskey, Molly C; Barrett, Lynn K; Maly, Dustin J; Ojo, Kayode K; Van Voorhis, Wes; Hemphill, Andrew (2017). Development of a murine vertical transmission model for Toxoplasma gondii oocyst infection and studies on the efficacy of bumped kinase inhibitor (BKI)-1294 and the naphthoquinone buparvaquone against congenital toxoplasmosis. Journal of antimicrobial chemotherapy, 72(8), pp. 2334-2341. Oxford University Press 10.1093/jac/dkx134 |
| ISSN: | 1460-2091 0305-7453 |
| DOI: | 10.1093/jac/dkx134 |
| Popis: | Objectives Establishment of a mouse model for congenital toxoplasmosis based on oral infection with oocysts from Toxoplasma gondii ME49 and its application for investigating chemotherapeutic options against congenital toxoplasmosis. Methods CD1 mice were mated, orally infected with 5, 25, 100, 500 or 2000 oocysts and monitored for clinical signs and survival of dams and pups until 4 weeks post partum . The parasite burden in infected mice was quantified by real-time PCR in lungs, brains and, in the case of surviving pups, also in eyes. Seroconversion was assessed by ELISA. T. gondii cysts in brain were identified by immunofluorescence. In a second experiment, pregnant CD1 mice challenged with 20 oocysts/mouse were treated with buparvaquone or the calcium-dependent protein kinase 1 inhibitor bumped kinase inhibitor (BKI)-1294 and the outcome of infection was analysed. Results T. gondii DNA was detected in the brain of all infected animals, irrespective of the infection dose. Seroconversion occurred at 3 weeks post-infection. Most pups born to infected dams died within 1 week post partum , but a small fraction survived until the end of the experiment. T. gondii DNA was detected in the brain of all survivors and half of them exhibited ocular infection. Chemotherapy with both compounds led to dramatically increased numbers of surviving pups and reduced cerebral infection. Most efficient were treatments with BKI-1294, with 100% survivors and only 7% brain-positive pups. Conclusions BKI-1294 and buparvaquone exert excellent activities against transplacental transmission in pregnant mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|