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Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica.

ABSTRACT: Oxidative stress is one of the strongest toxic factors in nature: it can harm or even kill cells. Cellular means of subverting the toxicity of oxidative stress are important for the success of infectious diseases. Many types of bacterium inhabit the intestine, where they can encounter pathogens. During oxidative stress, we analyzed the interplay between an intestinal parasite (the pathogenic amoeba Entamoeba histolytica - the agent of amoebiasis) and enteric bacteria (microbiome residents, pathogens and probiotics). We found that live enteric bacteria protected E. histolytica against oxidative stress. By high-throughput RNA sequencing, two amoebic regulatory modes were observed with enteric bacteria but not with probiotics. The first controls essential elements of homeostasis, and the second the levels of factors required for amoeba survival. Characteristic genes of both modes have been acquired by the amoebic genome through lateral transfer from the bacterial kingdom (e.g. glycolytic enzymes and leucine-rich proteins). Members of the leucine-rich are homologous to proteins from anti-bacterial innate immune such as Toll-like receptors. The factors identified here suggest that despite its old age in evolutionary terms, the protozoan E. histolytica displays key characteristics of higher eukaryotes' innate immune systems indicating that components of innate immunity existed in the common ancestor of plants and animals.

SUBMITTER: Varet H

PROVIDER: S-EPMC5998147 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica.

Varet Hugo H Shaulov Yana Y Sismeiro Odile O Trebicz-Geffen Meirav M Legendre Rachel R Coppée Jean-Yves JY Ankri Serge S Guillen Nancy N

Scientific reports 20180613 1

Oxidative stress is one of the strongest toxic factors in nature: it can harm or even kill cells. Cellular means of subverting the toxicity of oxidative stress are important for the success of infectious diseases. Many types of bacterium inhabit the intestine, where they can encounter pathogens. During oxidative stress, we analyzed the interplay between an intestinal parasite (the pathogenic amoeba Entamoeba histolytica - the agent of amoebiasis) and enteric bacteria (microbiome residents, patho ...[more]

PMID: 29899530

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Project description: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.IMPORTANCEEntamoeba 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.

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Project description:The protozoan parasite, Entamoeba histolytica, invades the host colon causing significant tissue destruction and inflammation. Upon host infection, the parasite is confronted with reactive oxygen and nitrogen species (ROS/RNS) that cause large-scale changes in gene expression profiles, which likely support the parasite's adaptation to the host environment. We have previously identified oxidative and nitrosative stress responsive genes using whole-genome expression profiling. Functional studies on two such genes are now reported and demonstrate that they have roles in parasite virulence. EHI_056680 encodes a small hypothetical protein named E. histolytica stress-induced adhesion factor (EhSIAF); EHI_188210 encodes a putative phospholipid transporting P-type ATPase/flippase (EhPTPA). Over-expression of each protein in E. histolytica trophozoites enhanced parasite survival in response to oxidative stress. Exposure to oxidative and nitrosative stress did not affect the localization of EhSIAF or EhPTPA but markedly increased EhPTPA protein levels. Interestingly, over-expression of each gene resulted in parasites with increased adherence to healthy mammalian cells, but increased adherence to apoptotic cells was noted only in EhSIAF over-expressing parasites. However, despite having increased adherence to both healthy and apoptotic host cells, EhSIAF-over-expressing parasites were reduced in their ability to destroy mammalian cell monolayers, raising the intriguing possibility that EhSIAF over-expression caused signaling defects or resulted in a dominant negative phenotype. Over-expression of EhSIAF and EhPTPA also resulted in decreased motility in a transwell motility assay. Thus, we have confirmed that two genes that are upregulated by ROS confer increased resistance to oxidative stress and have identified an unexpected role of EhSIAF and EhPTPA in host cell adherence and a role of EhSIAF in parasite virulence. Our data imply that stress response genes may play multi-factorial roles in amoebic pathogenesis.

Dataset Information

Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica.

Publications

Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica.

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