Recent advances in Entamoeba biology: RNA interference, drug discovery, and gut microbiome

Morgado, Pedro; Manna, Dipak; Singh, Upinder

doi:10.12688/f1000research.9241.1

Cited by 15 publications

(5 citation statements)

References 100 publications

(106 reference statements)

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“…Based on publications prior to growth of E. histolytica in axenic culture, an obvious potential explanation is simply that the bacteria prolong amebic survival by providing nutrition ( 55 ). However, it is now well established that E. histolytica infection is impacted by the intestinal microbiome and that bacteria alter E. histolytica cell signaling and transcriptomics ( 4 , 56 – 58 ). Thus, the effect of E. coli in this Matrigel environment could potentially regulate cellular processes relevant for amoebic migration and virulence and presents an avenue for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Coactosin Phosphorylation Controls Entamoeba histolytica Cell Membrane Protrusions and Cell Motility

Hasan

Teixeira

Lam

et al. 2020

mBio

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Invasion of the colon wall by Entamoeba histolytica during amoebic dysentery entails migration of trophozoites through tissue layers that are rich in extracellular matrix. Transcriptional silencing of the E. histolytica surface metalloprotease EhMSP-1 produces hyperadherent less-motile trophozoites that are deficient in forming invadosomes. Reversible protein phosphorylation is often implicated in regulation of cell motility and invadosome formation. To identify such intermediaries of the EhMSP-1-silenced phenotype, here we compared the phosphoproteomes of EhMSP-1-silenced and vector control trophozoites by using quantitative tandem mass spectrometry-based proteomics. Six proteins were found to be differentially phosphorylated in EhMSP-1-silenced and control cells, including EhCoactosin, a member of the ADF/cofilin family of actin-binding proteins, which was more frequently phosphorylated at serine 147. Regulated overexpression of wild-type, phosphomimetic, and nonphosphorylatable EhCoactosin variants was used to test if phosphorylation functions in control of E. histolytica actin dynamics. Each of the overexpressed proteins colocalized with F-actin during E. histolytica phagocytosis. Nonetheless, trophozoites overexpressing an EhCoactosin phosphomimetic mutant formed more and poorly coordinated cell membrane protrusions compared to those in control or cells expressing a nonphosphorylatable mutant, while trophozoites overexpressing nonphosphorylatable EhCoactosin were significantly more motile within a model of mammalian extracellular matrix. Therefore, although EhCoactosin’s actin-binding ability appeared unaffected by phosphorylation, EhCoactosin phosphorylation helps to regulate amoebic motility. These data help to understand the mechanisms underlying altered adherence and motility in EhMSP-1-silenced trophozoites and lay the groundwork for identifying kinases and phosphatases critical for control of amoebic invasiveness. IMPORTANCE Invasive amoebiasis, caused by the intestinal parasite Entamoeba histolytica, causes life-threatening diarrhea and liver abscesses, but, for unknown reasons, only approximately 10% of E. histolytica infections become symptomatic. A key requirement of invasion is the ability of the parasite to migrate through tissue layers. Here, we systematically looked for differences in protein phosphorylation between control parasites and a previously identified hyperadherent E. histolytica cell line that has reduced motility. We identified EhCoactosin, an actin-binding protein not previously known to be phosphoregulated, as one of the differentially phosphorylated proteins in E. histolytica and demonstrated that EhCoactosin phosphorylation functions in control of cell membrane dynamics and amoebic motility. This and the additional differentially phosphorylated proteins reported lay the groundwork for identifying kinases and phosphatases that regulate tissue invasiveness.

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Section: Discussionmentioning

confidence: 99%

Coactosin Phosphorylation Controls Entamoeba histolytica Cell Membrane Protrusions and Cell Motility

Hasan

Teixeira

Lam

et al. 2020

mBio

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“…This will enable us to reproduce the clinical manifestations observed in the human host in a better way. Moreover, the tools to knock out/downregulate gene expression can be enhanced (Morgado et al, 2016 ) by adapting CRISPR/Cas9 system to E. histolytica (Cui and Yu, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Utilization of Different Omic Approaches to Unravel Stress Response Mechanisms in the Parasite Entamoeba histolytica

Nagaraja

Ankri

2018

Front. Cell. Infect. Microbiol.

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During its life cycle, the unicellular parasite Entamoeba histolytica is challenged by a wide variety of environmental stresses, such as fluctuation in glucose concentration, changes in gut microbiota composition, and the release of oxidative and nitrosative species from neutrophils and macrophages. The best mode of survival for this parasite is to continuously adapt itself to the dynamic environment of the host. Our ability to study the stress-induced responses and adaptive mechanisms of this parasite has been transformed through the development of genomics, proteomics or metabolomics (omics sciences). These studies provide insights into different facets of the parasite's behavior in the host. However, there is a dire need for multi-omics data integration to better understand its pathogenic nature, ultimately paving the way to identify new chemotherapeutic targets against amebiasis. This review provides an integration of the most relevant omics information on the mechanisms that are used by E. histolytica to resist environmental stresses.

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“…Conversely, an association between Prevotella copri and Entamoeba has been observed in infected children [166]. This bacterium associates with gut inflammation and the generation of an excessive immunity in patients and animal models [167], suggesting that parasite infection is influenced by the inflammatory state of the gut, which is potentially associated with changes in the gut microbiome [168].…”

Section: Entamoeba Histolyticamentioning

confidence: 99%

“…In general, further microbiome studies may provide insights into why some patients get an invasive disease, which factors contribute to parasite-associated malnutrition and growth inhibition, and how E. histolytica may change gut flora [162,168].…”

Section: Entamoeba Histolyticamentioning

confidence: 99%

Host Invasion by Pathogenic Amoebae: Epithelial Disruption by Parasite Proteins

Betanzos

Bañuelos

Orozco

2019

Genes

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The epithelium represents the first and most extensive line of defence against pathogens, toxins and pollutant agents in humans. In general, pathogens have developed strategies to overcome this barrier and use it as an entrance to the organism. Entamoeba histolytica, Naegleria fowleri and Acanthamoeba spp. are amoebae mainly responsible for intestinal dysentery, meningoencephalitis and keratitis, respectively. These amoebae cause significant morbidity and mortality rates. Thus, the identification, characterization and validation of molecules participating in host-parasite interactions can provide attractive targets to timely intervene disease progress. In this work, we present a compendium of the parasite adhesins, lectins, proteases, hydrolases, kinases, and others, that participate in key pathogenic events. Special focus is made for the analysis of assorted molecules and mechanisms involved in the interaction of the parasites with epithelial surface receptors, changes in epithelial junctional markers, implications on the barrier function, among others. This review allows the assessment of initial host-pathogen interaction, to correlate it to the potential of parasite invasion.

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Recent advances in Entamoeba biology: RNA interference, drug discovery, and gut microbiome

Cited by 15 publications

References 100 publications

Coactosin Phosphorylation Controls Entamoeba histolytica Cell Membrane Protrusions and Cell Motility

Coactosin Phosphorylation Controls Entamoeba histolytica Cell Membrane Protrusions and Cell Motility

Utilization of Different Omic Approaches to Unravel Stress Response Mechanisms in the Parasite Entamoeba histolytica

Host Invasion by Pathogenic Amoebae: Epithelial Disruption by Parasite Proteins

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