Biology subjects

Hisaeda, H.

Publications and source records attributed to Hisaeda, H..

3 recordsLinked to original sources

bioRxiv2025

The gut microbiota-derived metabolite indole regulates cytoskeletal functions and virulence in Entamoeba histolytica

Entamoeba histolytica is a pathogenic amoeba that inhabits the human large intestine and causes amoebiasis. E. histolytica interacts with both the intestinal microbiota and the metabolites they produce. These bacterial metabolites play a crucial role in shaping the virulence and stress resistance of E. histolytica. One such metabolite, indole, is synthesized by bacteria from tryptophan and functions as a key signaling molecule. In this study, we investigated the impact of indole on E. histolytica by incubating trophozoites with the metabolite and performing proteomic analyses under various conditions, including trophozoites adapted to indole. Our results show that indole is toxic to E. histolytica, with an inhibitory concentration (IC) of 1.2 mM; however, the parasite can adapt to this concentration. Proteomic analyses reveal that indole-adapted trophozoites display enhanced resistance to oxidative stress (OS), upregulation of cytoskeletal proteins, and increased virulence. These trophozoites exhibit increased F-actin formation, smaller cell size, stronger adhesion to HeLa cells, enhanced migratory capacity, and more effective colonization of the mouse cecum compared to non-adapted trophozoites. Thus, indole exerts a dual effect on E. histolytica physiology. While indole is initially toxic to the parasite, adaptation to indole confers enhanced resistance to OS and promotes a more virulent phenotype. This duality underscores the complex role of microbiota-derived metabolites in modulating parasite behavior and highlights indole as a key microbial signal. Author summaryEntamoeba histolytica is a unicellular parasite living in the human large intestine and can cause a disease called amoebiasis. Inside the intestine, E. histolytica interacts with the microbiota and with the metabolites they produce. One such metabolite is indole, which is produced by gut bacteria from tryptophan and used by human cells and trophozoites. In this study, we explored how indole affects E. histolytica. We found that indole is toxic to the parasite at first, but over time, the amoeba can adapt and survive in its presence. Using protein analysis techniques, we discovered that indole-adapted amoebas become more resistant to stress and more virulent. They produce more F-actin, leading to improved mobility, degrade more HeLa cells, and colonize the gut of mice more efficiently than wild-type amoebas (WT). These results show that, while indole initially harms the parasite, it also triggers changes that make it more resistant to stress and more virulent. Our work highlights how metabolites produced by bacteria in the large intestine can influence the behavior of E. histolytica.

microbiology↗

bioRxiv2021

Malaria parasite evades mosquito immunity by glutaminyl cyclase mediated protein modification

Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of Plasmodium QC. We show that Plasmodium sporozoites of QC-null mutants are recognized by the mosquito immune system and melanized when they reach the hemocoel. Sporozoite numbers in salivary glands are also reduced in mosquitoes infected with QC-null or QC catalytically-dead mutants. This phenotype can be rescued by genetic complementation or by disrupting mosquito hemocytes or melanization immune responses. Mutation of a single QC-target glutamine of the major sporozoite surface protein (CSP) also results in immune recognition of sporozoites. These findings reveal QC-mediated post-translational modification of surface proteins as a major mechanism of mosquito immune evasion by Plasmodium sporozoites.

microbiology↗

bioRxiv2020

Queuine is a nutritional regulator of Entamoeba histolytica response to oxidative stress and a virulence attenuator

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 tRNAAspGUC. 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 OS response, such as heat shock protein 70 (Hsp 70), 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 tRNAAspGUC, 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 the 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 a 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.

microbiology↗