RT Journal Article
T1 Neospora caninum: Differential Proteome of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294
A1 Winzer, Pablo
A1 Müller, Joachim
A1 Imhof, Dennis
A1 Ritler, Dominic
A1 Uldry, Anne-Christine
A1 Braga-Lagache, Sophie
A1 Heller, Manfred
A1 Ojo, Kayode K.
A1 Van Voorhis, Wesley C.
A1 Ortega Mora, Luis Miguel
A1 Hemphill, Andrew
AB Background: the apicomplexan parasite Neospora caninum causes important reproductive problems in farm animals, most notably in cattle. After infection via oocysts or tissue cysts, rapidly dividing tachyzoites infect various tissues and organs, and in immunocompetent hosts, they differentiate into slowly dividing bradyzoites, which form tissue cysts and constitute a resting stage persisting within infected tissues. Bumped kinase inhibitors (BKIs) of calcium dependent protein kinase 1 are promising drug candidates for the treatment of Neospora infections. BKI-1294 exposure of cell cultures infected with N. caninum tachyzoites results in the formation of massive multinucleated complexes (MNCs) containing numerous newly formed zoites, which remain viable for extended periods of time under drug pressure in vitro. MNC and tachyzoites exhibit considerable antigenic and structural differences. Methods: Using shotgun mass spectrometry, we compared the proteomes of tachyzoites to BKI-1294 induced MNCs, and analyzed the mRNA expression levels of selected genes in both stages. Results: More than half of the identified proteins are downregulated in MNCs as compared to tachyzoites. Only 12 proteins are upregulated, the majority of them containing SAG1 related sequence (SRS) domains, and some also known to be expressed in bradyzoites Conclusions: MNCs exhibit a proteome different from tachyzoites, share some bradyzoite-like features, but may constitute a third stage, which remains viable and ensures survival under adverse conditions such as drug pressure. We propose the term “baryzoites” for this stage (from Greek βα%υσ = massive, bulky, heavy, inert).
PB MDPI
SN 2076-2607
YR 2020
FD 2020-05-26
LK https://hdl.handle.net/20.500.14352/8053
UL https://hdl.handle.net/20.500.14352/8053
LA eng
NO Swiss National Science Foundation (SNF)
NO National Institutes of Health (NIH)
DS Docta Complutense
RD 3 may 2024