Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator

ABSTRACT Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Her...

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Autores principales:	Shruti Nagaraja, Maggi W. Cai, Jingjing Sun, Hugo Varet, Lotem Sarid, Meirav Trebicz-Geffen, Yana Shaulov, Mohit Mazumdar, Rachel Legendre, Jean-Yves Coppée, Thomas J. Begley, Peter C. Dedon, Samudrala Gourinath, Nancy Guillen, Yumiko Saito-Nakano, Chikako Shimokawa, Hajime Hisaeda, Serge Ankri
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Entamoeba histolytica oxidative stress tRNA modification virulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/497ef5cb0f7e4ff8a51086e7aee30122
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spelling	oai:doaj.org-article:497ef5cb0f7e4ff8a51086e7aee301222021-11-10T18:37:48ZQueuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator10.1128/mBio.03549-202150-7511https://doaj.org/article/497ef5cb0f7e4ff8a51086e7aee301222021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.03549-20https://doaj.org/toc/2150-7511ABSTRACT Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in [Formula: see text]. Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in [Formula: see text], parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence. IMPORTANCE Entamoeba histolytica is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota. The gut flora is implicated in the onset of symptomatic amebiasis due to alterations in the composition of bacteria. These bacteria modulate the physiology of the parasite and affect the virulence of the parasite through unknown mechanisms. Queuine, a modified nucleobase of queuosine, is exclusively produced by the gut bacteria and leads to tRNA modification at the anticodon loops of specific tRNAs. We found that queuine induces mild oxidative stress resistance in the parasite and attenuates its virulence. Our study highlights the importance of bacterially derived products in shaping the physiology of the parasite. The fact that queuine inhibits the virulence of E. histolytica may lead to new strategies for preventing and/or treating amebiasis by providing to the host queuine directly or via probiotics.Shruti NagarajaMaggi W. CaiJingjing SunHugo VaretLotem SaridMeirav Trebicz-GeffenYana ShaulovMohit MazumdarRachel LegendreJean-Yves CoppéeThomas J. BegleyPeter C. DedonSamudrala GourinathNancy GuillenYumiko Saito-NakanoChikako ShimokawaHajime HisaedaSerge AnkriAmerican Society for MicrobiologyarticleEntamoeba histolyticaoxidative stresstRNA modificationvirulenceMicrobiologyQR1-502ENmBio, Vol 12, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Entamoeba histolytica oxidative stress tRNA modification virulence Microbiology QR1-502
spellingShingle	Entamoeba histolytica oxidative stress tRNA modification virulence Microbiology QR1-502 Shruti Nagaraja Maggi W. Cai Jingjing Sun Hugo Varet Lotem Sarid Meirav Trebicz-Geffen Yana Shaulov Mohit Mazumdar Rachel Legendre Jean-Yves Coppée Thomas J. Begley Peter C. Dedon Samudrala Gourinath Nancy Guillen Yumiko Saito-Nakano Chikako Shimokawa Hajime Hisaeda Serge Ankri Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator
description	ABSTRACT Queuosine is a naturally occurring modified ribonucleoside found in the first position of the anticodon of the transfer RNAs for Asp, Asn, His, and Tyr. Eukaryotes lack pathways to synthesize queuine, the nucleobase precursor to queuosine, and must obtain it from diet or gut microbiota. Here, we describe the effects of queuine on the physiology of the eukaryotic parasite Entamoeba histolytica, the causative agent of amebic dysentery. Queuine is efficiently incorporated into E. histolytica tRNAs by a tRNA-guanine transglycosylase (EhTGT) and this incorporation stimulates the methylation of C38 in [Formula: see text]. Queuine protects the parasite against oxidative stress (OS) and antagonizes the negative effect that oxidation has on translation by inducing the expression of genes involved in the OS response, such as heat shock protein 70 (Hsp70), antioxidant enzymes, and enzymes involved in DNA repair. On the other hand, queuine impairs E. histolytica virulence by downregulating the expression of genes previously associated with virulence, including cysteine proteases, cytoskeletal proteins, and small GTPases. Silencing of EhTGT prevents incorporation of queuine into tRNAs and strongly impairs methylation of C38 in [Formula: see text], parasite growth, resistance to OS, and cytopathic activity. Overall, our data reveal that queuine plays a dual role in promoting OS resistance and reducing parasite virulence. IMPORTANCE Entamoeba histolytica is a unicellular parasite that causes amebiasis. The parasite resides in the colon and feeds on the colonic microbiota. The gut flora is implicated in the onset of symptomatic amebiasis due to alterations in the composition of bacteria. These bacteria modulate the physiology of the parasite and affect the virulence of the parasite through unknown mechanisms. Queuine, a modified nucleobase of queuosine, is exclusively produced by the gut bacteria and leads to tRNA modification at the anticodon loops of specific tRNAs. We found that queuine induces mild oxidative stress resistance in the parasite and attenuates its virulence. Our study highlights the importance of bacterially derived products in shaping the physiology of the parasite. The fact that queuine inhibits the virulence of E. histolytica may lead to new strategies for preventing and/or treating amebiasis by providing to the host queuine directly or via probiotics.
format	article
author	Shruti Nagaraja Maggi W. Cai Jingjing Sun Hugo Varet Lotem Sarid Meirav Trebicz-Geffen Yana Shaulov Mohit Mazumdar Rachel Legendre Jean-Yves Coppée Thomas J. Begley Peter C. Dedon Samudrala Gourinath Nancy Guillen Yumiko Saito-Nakano Chikako Shimokawa Hajime Hisaeda Serge Ankri
author_facet	Shruti Nagaraja Maggi W. Cai Jingjing Sun Hugo Varet Lotem Sarid Meirav Trebicz-Geffen Yana Shaulov Mohit Mazumdar Rachel Legendre Jean-Yves Coppée Thomas J. Begley Peter C. Dedon Samudrala Gourinath Nancy Guillen Yumiko Saito-Nakano Chikako Shimokawa Hajime Hisaeda Serge Ankri
author_sort	Shruti Nagaraja
title	Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator
title_short	Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator
title_full	Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator
title_fullStr	Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator
title_full_unstemmed	Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator
title_sort	queuine is a nutritional regulator of <named-content content-type="genus-species">entamoeba histolytica</named-content> response to oxidative stress and a virulence attenuator
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/497ef5cb0f7e4ff8a51086e7aee30122
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Queuine Is a Nutritional Regulator of <named-content content-type="genus-species">Entamoeba histolytica</named-content> Response to Oxidative Stress and a Virulence Attenuator

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