Neospora caninum: Differential Proteome of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294.

Winzer, Pablo; Müller, Joachim; Imhof, Dennis; Ritler, Dominic; Uldry, Anne-Christine; Braga-Lagache, Sophie; Heller, Manfred; Ojo, Kayode K; Van Voorhis, Wesley C; Ortega-Mora, Luis-Miguel; Hemphill, Andrew (2020). Neospora caninum: Differential Proteome of Multinucleated Complexes Induced by the Bumped Kinase Inhibitor BKI-1294. Microorganisms, 8(6) MDPI 10.3390/microorganisms8060801

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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 βαρυσ = massive, bulky, heavy, inert).

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Massenspektrometrie- und Proteomics-Labor
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Protein- und Zellbiologie

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Winzer, Pablo Arnold; Müller, Joachim; Imhof, Dennis; Ritler, Dominic; Uldry, Anne-Christine; Braga, Sophie Marie-Pierre; Heller, Manfred and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

2076-2607

Publisher:

MDPI

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

28 Dec 2020 17:38

Last Modified:

28 Dec 2020 17:38

Publisher DOI:

10.3390/microorganisms8060801

PubMed ID:

32466554

Uncontrolled Keywords:

antigenic variation chemotherapy drug adaptation drug resistance

BORIS DOI:

10.48350/150164

URI:

https://boris.unibe.ch/id/eprint/150164

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