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36. NcGRA7 and NcROP40 Play a Role in the Virulence of Neospora caninum in a Pregnant Mouse Model

Author

Rico-San Román, Laura, Amieva, Rafael, Regidor-Cerrillo, Javier, García-Sánchez, Marta, Collantes-Fernández, Esther, Pastor-Fernández, Iván, Saeij, Jeroen PJ, Ortega-Mora, Luis Miguel, and Horcajo, Pilar

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Vaccine Related, Biodefense, Neurosciences, Prevention, Infectious Diseases, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being, BALB/c, CRISPR/Cas9, NcGRA7 protein, NcROP40 protein, Neospora caninum, pregnant mouse model, virulence factor, Microbiology, Medical microbiology
Abstract

The intraspecific variability among Neospora caninum isolates in their in vitro behaviour and in vivo virulence has been widely studied. In particular, transcriptomic and proteomic analyses have shown a higher expression/abundance of specific genes/proteins in high-virulence isolates. Consequently, the dense granule protein NcGRA7 and the rhoptry protein NcROP40 were proposed as potential virulence factors. The objective of this study was to characterize the role of these proteins using CRISPR/Cas9 knockout (KO) parasites in a well-established pregnant BALB/c mouse model of N. caninum infection at midgestation. The deletion of NcGRA7 and NcROP40 was associated with a reduction of virulence, as infected dams displayed milder clinical signs, lower parasite burdens in the brain, and reduced mortality rates compared to those infected with the wild-type parasite (Nc-Spain7). Specifically, those infected with the NcGRA7 KO parasites displayed significantly milder clinical signs and a lower brain parasite burden. The median survival time of the pups from dams infected with the two KO parasites was significantly increased, but differences in neonatal mortality rates were not detected. Overall, the present study indicates that the disruption of NcGRA7 considerably impairs virulence in mice, while the impact of NcROP40 deletion was more modest. Further research is needed to understand the role of these virulence factors during N. caninum infection.

Published
2022

47. Introduction

Author

del Pilar Chouza-Calo, María, primary, Fernández, Esther, additional, and Thacker, Jonathan, additional

Published
2023
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