Logo image
Back
The NAD+Responsive Transcription Factor ERM-BP Functions Downstream of Cellular Aggregation and Is an Early Regulator of Development and Heat Shock Response inEntamoeba
Journal article   Peer reviewed

The NAD+Responsive Transcription Factor ERM-BP Functions Downstream of Cellular Aggregation and Is an Early Regulator of Development and Heat Shock Response inEntamoeba

Dipak Manna, Daniela Lozano-Amado, Gretchen Ehrenkaufer and Upinder Singh
Frontiers in cellular and infection microbiology, Vol.10, 363
07/17/2020
DOI: 10.3389/fcimb.2020.00363
PMID: 32766170
url
https://doi.org/10.3389/fcimb.2020.00363View
Published (Version of record) Open Access

Abstract

Entamoeba histolyticais a protozoan parasite and a major cause of dysentery and diarrheal disease in developing countries. Disease transmission from one host to another occurs via cysts which can survive in environmental extremes and are transmitted through contaminated food and water. Recent studies in our lab identified a novel transcription factor, Encystation Regulatory Motif- Binding Protein (ERM-BP), which is responsive to NAD(+)and has an important role in encystation. The key residues important for ERM-BP function were demonstratedin vitrousing recombinant protein. In this study we demonstrate thein vivofunctional consequences of mutations in key domains and their impact onEntamoebaencystation. Our results show that mutations in the DNA binding domain (ERM-BP-DBM) and in the nicotinamidase domain (ERM-BP-C198A) lead to protein mis-localization in both trophozoites and cysts and significantly reduce encystation efficiency. Additionally, we showed that silencing of ERM-BP significantly decreased the size and number of multi-nucleated giant cells (MGC) that form during encystation, indicating that ERM-BP functions upstream of the cellular aggregation that precedes stage conversion. Dissection of epistatic interactions between ERM-BP and a second encystation-related transcription factor, NF-Y revealed that ERM-BP is upstream of NF-Y in controlling the developmental cascade and appears to be one of the earliest regulators of development identified to date inEntamoeba. We also demonstrated that ERM-BP is upregulated during heat stress inEntamoeba, another condition which increases intracellular NAD(+)levels and that overexpression of ERM-BP makesE. histolyticaandE. invadensparasites more resistant to heat stress. Overexpression of ERM-BP inE. histolyticaalso induced the formation of cyst-like quadrinucleated cells and formation of MGCs. Overall, our work has identified an important role of ERM-BP inEntamoebastress response and links an NAD(+)-responsive transcription factor to both development and heat shock response. Characterization of stress and developmental cascades are important avenues to investigate forEntamoeba, an important human parasitic pathogen.
 Immunology Life Sciences & Biomedicine Microbiology Science & Technology

Details

Metrics

1 Record Views
14 Times Cited - Web of Science
Logo image