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Queuine Is a Nutritional Regulator of Entamoeba histolytica 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. 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.

SUBMITTER: Nagaraja S

PROVIDER: S-EPMC8092309 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Characterization of the human microbiota is providing new insightsinto the complexity of host–parasite–bacterium relationships. Amoebiasis (an intestinal infection affecting a large proportion of the population in many countries worldwide) is caused by the amoebic parasite Entamoeba histolytica. During amoebiasis, the parasite encounters several types of stress as a result of the host’s response to infection. Given that E. histolytica phagocytises bacteria in the intestinal lumen, we hypothesized that enteric bacteria can influence the course of an amoebic infection. Hence, we used live Escherichia coli O55 as a pertinent model of the bacterial community’s contribution to amoebic responses during host- induced stress. By measuring amoebic survival, we found that live E. coli protected E. histolytica against oxidative stress (OS) but not against nitrosative stress. E. coli– associated protection is correlated with massive transcriptionalchanges in amoebic genes acquired through lateral transfer from the bacterial kingdom, including genes coding for proteinscontaining leucine-rich repeat (LRR) motifs. The transcriptome profile triggered by OS and E. coli was also observed with other enteric bacteria, including pathogens and non-pathogens. In contrast, exposure to a probiotic resulted in a different transcriptome profile. The present study shows that OS and live bacteria together modulate 84 of E. histolytica’s 137 LRR protein genes. The LRR proteins are involvedin protein-ligand and protein-protein interactions – especially in proteins that interact with bacteria as part of the innate immune response in mammals and plants, such as Toll-like receptors. The structural and functional homology of LRRs and TLRs identified here suggest that despite its old age in evolutionary terms, the protozoan E. histolytica displays key characteristics of higher eukaryotes’ innate immune systems. We conclude that components of innate immunity existed in the common ancestor of plants and animals

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Queuine Is a Nutritional Regulator of Entamoeba histolytica Response to Oxidative Stress and a Virulence Attenuator.

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