Transcriptome Analysis of Entamoeba histolytica Trophozoites during in vivo Contact-independent Mediated Host-parasite Interaction: Putative Pathways Related to PCD
David Guillermo Pérez Ishiwara *
Laboratorio de Biomedicina Molecular I, ENMYH, Instituto Politécnico Nacional, CP07320, Mexico.
Mineko Shibayama
Departamento de Infectómica y Patogénesis Molecular, CINVESTAV-IPN, CP 07360, Mexico.
Kumiko Nakada-Tsukui
Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
Ghulam Jeelani
Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640, Japan.
María del Consuelo Gómez-García
Laboratorio de Biomedicina Molecular I, ENMYH, Instituto Politécnico Nacional, CP07320, Mexico.
Olivia Medel Flores
Laboratorio de Biomedicina Molecular I, ENMYH, Instituto Politécnico Nacional, CP07320, Mexico.
Tomoyoshi Nozaki *
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Japan.
*Author to whom correspondence should be addressed.
Abstract
Aim: In the present study, we exploited DNA microarray-based transcriptome analysis and showed overall changes in gene expression in vivo of amoebic trophozoites that interact with animal soluble factors using an intraperitoneal dialysis bag model to elucidate putative molecular pathways and genes involved in this interaction.
Study Design: We exploited DNA microarray-based transcriptome analysis.
Results: An analysis from a network including the interactions of up-regulated genes and their neighbors revealed the presence of 11 functionally related modules. Six of the modules obtained were related to endoplasmic reticulum (ER) functions, such as degradation, stress, proteasome-ubiquitination, phosphorylation, lipid metabolism, and protein sorting. Furthermore, major transcriptional changes displayed by the parasite at the beginning of interaction were attributed to the response to the host defense. These data are consistent with the notion that the concerted expression of genes necessary for survival such as increment in protein synthesis, cytoskeleton rearrangement, vesicular traffic and genes involved in cell death including calcium imbalance and the ER signals associated with protein degradation (ERAD) is an overall landscape during the in vivo interaction between the amoebic trophozoites and animal soluble factors, and suggest that the ER stress is one of the main pathways leading to programmed cell death in E. histolytica.
Conclusion: The present findings on the global transcriptional changes displayed by the parasite at the early stages of interaction with host environments in peritoneal implantation indicate that a substantial proportion of concerted changes in gene expression in amoebic trophozoites are attributable to the parasite’s response for cell death signals due to ER stress. A detailed knowledge of the underlying molecular mechanism might suggest the efficient elimination of this parasite by promoting their death pathways.
Keywords: Microarrays, E. histolytica, ER stress, programmed cell death, transcriptome, in vivo model