Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins

Ng, Yee Ling; Olivos-García, Alfonso; Lim, Teck Kwang; Noordin, Rahmah; Lin, Qingsong; Othman, Nurulhasanah

doi:10.4269/ajtmh.18-0415

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…However, the replicates of serum starved showed larger variation compared to control replicates. Our proteome analysis covered a much larger number of proteins from E. histolytica trophozoites as compared to the previous studies (1029, 1307, and 1531 proteins, respectively) [28–30]. Larger depth of protein coverage is likely to improve our analysis of protein abundance changes in E. histolytica .…”

Section: Resultsmentioning

confidence: 99%

Multi‐omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress

et al. 2022

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Entamoeba histolytica is responsible for dysentery and extraintestinal disease in humans. To establish successful infection, it must generate adaptive response against stress due to host defense mechanisms. We have developed a robust proteomics workflow by combining miniaturized sample preparation, low flow-rate chromatography, and ultra-high sensitivity mass spectrometry, achieving increased proteome coverage, and further integrated proteomics and RNA-seq data to decipher regulation at translational and transcriptional levels. Label-free quantitative proteomics led to identification of 2344 proteins, an improvement over the maximum number identified in E. histolytica proteomic studies. In serum-starved cells, 127 proteins were differentially abundant and were associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport. The virulence factor, Gal/GalNAc-inhibitable lectin subunits, was significantly altered. Integration of transcriptomic and proteomic data revealed that only 30% genes were coordinately regulated at both transcriptional and translational levels. Some highly expressed transcripts did not change in protein abundance. Conversely, genes with no transcriptional change showed enhanced protein abundance, indicating post-transcriptional regulation. This multi-omics approach enables more refined gene expression analysis to understand the adaptive response of E. histolytica during growth stress.

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Section: Resultsmentioning

confidence: 99%

Multi‐omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress

et al. 2022

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“…It is able to induce a host immune response. Furthermore, during the initial stage of the infection, increased expression of this parasite protein can be seen [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…The Rho family GTPase protein (EHI_129750) and 70 kDa heat shock protein putative (EHI_199590) were increased in abundance, while its isoforms Rho family GTPase (EHI_192450 and EHI_146180) and heat shock protein 70 putative (EHI_052860) were decreased in abundance by comparing the two fractions. The 70 kDa heat shock protein and Rho family GTPase family proteins play important roles in the virulence of the parasite together with other identified proteins, for example, Gal/GalNAc subunit, NAD(P) transhydrogenase alpha and calreticulin [ 9 ]. From the functional classification analysis, Rho family GTPase (EHI_129750) is involved in catalytic activity and binding and increased abundance of GTPase proteins may give a possibility of effective colonization and invasion of the trophozoites in the host [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Entamoeba histolytica: Proteomics Bioinformatics Reveal Predictive Functions and Protein–Protein Interactions of Differentially Abundant Membrane and Cytosolic Proteins

Azmi

Othman

2021

Membranes

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Amoebiasis is caused by Entamoeba histolytica and ranked second for parasitic diseases causing death after malaria. E. histolytica membrane and cytosolic proteins play important roles in the pathogenesis. Our previous study had shown several cytosolic proteins were found in the membrane fraction. Therefore, this study aimed to quantify the differential abundance of membrane and cytosolic proteins in membrane versus cytosolic fractions and analyze their predicted functions and interaction. Previous LC-ESI-MS/MS data were analyzed by PERSEUS software for the differentially abundant proteins, then they were classified into their functional annotations and the protein networks were summarized using PantherDB and STRiNG, respectively. The results showed 24 (44.4%) out of the 54 proteins that increased in abundance were membrane proteins and 30 were cytosolic proteins. Meanwhile, 45 cytosolic proteins were found to decrease in abundance. Functional analysis showed differential abundance proteins involved in the molecular function, biological process, and cellular component with 18.88%, 33.04% and, 48.07%, respectively. The STRiNG server predicted that the decreased abundance proteins had more protein–protein network interactions compared to increased abundance proteins. Overall, this study has confirmed the presence of the differentially abundant membrane and cytosolic proteins and provided the predictive functions and interactions between them.

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“…In E. histolytica , a protozoan parasite that causes amebiasis, Calr (EhCalr) participates in several roles related to the host-immune modulation. Quantitative proteomic analysis and an ex vivo modeling indicates that EhCalr is an abundant membrane protein expressed in virulent variants ( 75 , 76 ). EhCalr, from pathogenic and non-pathogenic species, binds C1 and inhibits the CP activation ( 63 ).…”

Section: Calreticulin In Other Parasitic Infectionsmentioning

confidence: 99%

The Interactions of Parasite Calreticulin With Initial Complement Components: Consequences in Immunity and Virulence

et al. 2020

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Because of its capacity to increase a physiologic inflammatory response, to stimulate phagocytosis, to promote cell lysis and to enhance pathogen immunogenicity, the complement system is a crucial component of both the innate and adaptive immune responses. However, many infectious agents resist the activation of this system by expressing or secreting proteins with a role as complement regulatory, mainly inhibitory, proteins. Trypanosoma cruzi, the causal agent of Chagas disease, a reemerging microbial ailment, possesses several virulence factors with capacity to inhibit complement at different stages of activation. T. cruzi calreticulin (TcCalr) is a highly-conserved, endoplasmic reticulum-resident chaperone that the parasite translocates to the extracellular environment, where it exerts a variety of functions. Among these functions, TcCalr binds C1, MBL and ficolins, thus inhibiting the classical and lectin pathways of complement at their earliest stages of activation. Moreover, the TcCalr/C1 interaction also mediates infectivity by mimicking a strategy used by apoptotic cells for their removal. More recently, it has been determined that these Calr strategies are also used by a variety of other parasites. In addition, as reviewed elsewhere, TcCalr inhibits angiogenesis, promotes wound healing and reduces tumor growth. Complement C1 is also involved in some of these properties. Knowledge on the role of virulence factors, such as TcCalr, and their interactions with complement components in host-parasite interactions, may lead toward the description of new anti-parasite therapies and prophylaxis.

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Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins

Cited by 11 publications

References 53 publications

Multi‐omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress

Multi‐omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress

Entamoeba histolytica: Proteomics Bioinformatics Reveal Predictive Functions and Protein–Protein Interactions of Differentially Abundant Membrane and Cytosolic Proteins

The Interactions of Parasite Calreticulin With Initial Complement Components: Consequences in Immunity and Virulence

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