AUTHOR=Velásquez Zahady D. , López-Osorio Sara , Mazurek Sybille , Hermosilla Carlos , Taubert Anja 

TITLE=Eimeria bovis Macromeront Formation Induces Glycolytic Responses and Mitochondrial Changes in Primary Host Endothelial Cells

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.703413

DOI=10.3389/fcimb.2021.703413

ISSN=2235-2988

ABSTRACT=Eimeria bovis is an intracellular apicomplexan parasite that causes considerable economic losses in the cattle industry worldwide. During the first merogony, E. bovis forms large macromeronts with >140,000 merozoites I in host endothelial cells. Since this is a high-energy demanding process, E. bovis exploits the host cellular metabolism to fulfil its metabolic requirements. We here analyzed the carbohydrate-related energetic metabolism of E. bovis-infected primary bovine umbilical vein endothelial cells during first merogony and showed that E. bovis infection indeed causes considerable changes in metabolic signatures, glycolytic and mitochondrial responses. Thus, an increase in both, oxygen consumption rates (OCR) and extracellular acidification rates (ECAR) were found in E. bovis-infected host cells indicating a shift from quiescent to energetic cell status. Enhanced levels of glucose and pyruvate consumption in addition to increased lactate production indicated a pivotal role of glycolysis in infected cells from 12 days p. i. onwards. This was confirmed by glycolytic inhibitors (2-DG, FDG) which indeed blocked macromeront development and diminished merozoite I production. As an interesting finding, we observed that 2-DG treatments boosted sporozoite egress. Referring to mitochondrial activities, intracellular ROS production was increased towards the end of merogony and mitochondrial potential was found enhanced from 12 d p. i. onwards. Besides, morphological alterations of membrane potential signals also indicated mitochondrial dysfunction in macromeront-carrying host endothelial cells.