Project #19238
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#19238 : Virulence and natural anti-sense RNA in Entamoeba histolytica, the agent of human amoebiasis
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Name of Applicant : Nancy GUILLEN
Date of application : 01-06-2022
Unit : Bioimage Analysis,Biology of Host-parasite Interactions
Location : Calmette, 1 etage
Phone : 0145688675
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Project context and summary :

Several evolutionary processes influence microbes virulence, a process ending with damage impacting host survival. Parasites are favored to exploit their hosts prudently to prolong infection in general overcoming the host immune response and avoid killing the host. Parasites also need to use some host resources to reproduce and transmit infections to new hosts. We are interested in parasites affecting humans as Entamoeba histolytica, which is a protozoan parasite and an amitochondriate pathogenic amoeba, which causes amoebiasis (dysentery and liver abscess). In addition to E. histolytica several species infect the human intestine although these do not cause disease and include in most of cases E. dispar and ocassionnally E. moshkovskii. A phylogenetically close Entamoeba, E. invadens infecting snails, is used as cellular model for Entamoeba cyst formation. Supported by the National Agency for Research (ANR-10-GENM-0011) we developed a project to firstly study the phenotype of pathogenic E. histolytica. In collaboration with the Hub we discovered that roughly half of ORFs present anti-sense RNAs (NATs) that map to the 3‘ end of genes. Their nature is modified upon environmental changes. The regulation of NATs is basically governed by genomic sequences within the very short intragenic region of the amoeba compact genome. Secondly, we determined phenotypic differences between Entamoeba species using comparative transcriptomics approaches. The species of Entamoeba infecting humans have common NATs profiles which are different from environmental species. Altogether the data has been compiled in two recently published papers. Previous studies comparing amoebae from the same species but modified for the expression of given virulence factors or exhibiting attenuated virulence as well as from non-pathogenic Entamoeba species indicates: (I) Trophozoites progressively lose their virulence in axenic culture, virulence maintenance requires regular contact with the host. (II) Tissue destruction and survival in target organs rely on a strong adaptive response, achieved by the regulation of the expression of specific parasite genes, encoding potential virulence factors. To further understand the pathogenic process leading to amoebiasis in humans, we are asking on the role of NATs in the adaptative behaviour of E. histolytica. In collaboration with the Hub we plan to attempt to answer this question taking advantage from the tools that we have already developed for the analysis of NATs. Transcriptomes will be analysed from trophozoites growing in culture during several months and at the same time, upon incubation of these trophozoites with human cells.

Related team publications :
1. Mornico D, Hon CC, Koutero M, Weber C, Coppée JY, Clark CG, Dillies MA, Guillen N. 2022. RNA Sequencing Reveals Widespread Transcription of Natural Antisense RNAs in Entamoeba Species. Microorganisms. Feb 8;10(2):396. doi: 10.3390/microorganisms10020396.
2. Mornico D, Hon CC, Koutero M, Weber C, Coppee JY, Dillies MA, Guillen N. 2020. Genomic determinants for initiation and length of natural antisense transcripts in Entamoeba histolytica. Sci Rep. Nov 19;10(1):20190. doi: 10.1038/s41598-020-77010-4.
3. Varet H, Shaulov Y, Sismeiro O, Trebicz-Geffen M, Legendre R, Coppée JY, Ankri S, Guillen N. 2018. Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica. Sci Rep. Jun 13;8(1):9042. doi: 10.1038/s41598-018-27086-w.
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Status : In Progress

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