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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Encephalitozoon microsporidia modulates p53-mediated apoptosis in infected cells
C del Aguila1, F Izquierdo, A G Granja
1Laboratorio de Parasitología, Facultad de Farmacia, Universidad San Pablo-CEU, Urbanización Montepríncipe, 28668 Boadilla del Monte, Madrid, Spain. cagupue@ceu.es
Abstract:
Microsporidia are intracellular obligate parasites which have recently been found to be related to fungi. They have a unique extrusion apparatus that is able to inject the sporoplasm directly into the target cell without using receptors. Encephalitozoon microsporidia are a source of morbidity and mortality in humans. It has been suggested that microsporidia may modulate the host cell cycle and apoptosis. We report here that caspase-3 cleavage is inhibited at different times of Vero cell infection by Encephalitozoon microsporidia and that the phosphorylation and translocation of p53 to the nucleus, previous steps for the activation of this protein, do not occur after infection of Vero cells. Consequently, the transcriptional function of p53 is impaired during the infection cycle as demonstrated by luciferase reporter assays. Thus, to our knowledge, for the first time it is shown that an intracellular parasite may be able to multiply in the host cell without activating the p53 apoptotic pathway of that cell. However, changes in the expression of Bcl-2 or Bax levels were not observed.
Insights
Encephalitozoon microsporidia inhibit host cell apoptosis by blocking p53 activation. This study shows intracellular parasites can multiply without triggering the p53 apoptotic pathway, a novel finding in parasite-host interactions.
Area of Science:
- * Mycology
- * Parasitology
- * Cell Biology
Background:
- * Microsporidia are obligate intracellular parasites related to fungi.
- * Encephalitozoon species cause significant human illness.
- * Microsporidia may influence host cell cycle regulation and apoptosis.
Purpose of the Study:
- * To investigate the effect of Encephalitozoon microsporidia infection on host cell apoptosis.
- * To determine if microsporidia interfere with the p53 signaling pathway.
Main Methods:
- * Vero cells were infected with Encephalitozoon microsporidia.
- * Caspase-3 cleavage was assessed.
- * p53 phosphorylation, nuclear translocation, and transcriptional activity (via luciferase assays) were analyzed.
Main Results:
- * Caspase-3 cleavage was inhibited during infection.
- * p53 phosphorylation and nuclear translocation were prevented.
- * p53 transcriptional function was impaired, preventing apoptosis induction.
Conclusions:
- * Encephalitozoon microsporidia actively inhibit the p53-mediated apoptotic pathway in host cells.
- * This is the first demonstration of an intracellular parasite multiplying without activating host cell p53 apoptosis.
- * No changes in Bcl-2 or Bax expression were observed.
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