Iron-Modulated Virulence Factors of
            <i>Entamoeba Histolytica</i>

Gastelum-Martínez, Aurora Alicia; León-Sicairos, Claudia; Plata-Guzmán, Laura Yuliana; Soto-Castro, Liliana; León-Sicairos, Nidia; Garza, Mireya de la

doi:10.2217/fmb-2018-0066

Cited by 12 publications

(9 citation statements)

References 77 publications

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“…To determine the effect of iron, growth kinetics were carried out at different iron concentrations. We observed a drastic reduction in the number of Giardia trophozoites without iron supplementation, which indicates that this parasite requires this metal in order to grow; this also occurs in other pathogens [ 18 , 21 , 26 , 28 , 47 , 48 , 49 ]. It would be interesting to study iron chelation as a chemotherapeutic alternative in Giardia growth under different iron conditions.…”

Section: Discussionmentioning

confidence: 70%

Stem–Loop Structures in Iron-Regulated mRNAs of Giardia duodenalis

Plata-Guzmán

Arroyo

León-Sicairos

et al. 2023

IJERPH

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Giardia duodenalis is a significant cause of waterborne and foodborne infections, day-care center outbreaks, and traveler’s diarrhea worldwide. In protozoa such as Trichomonas vaginalis and Entamoeba histolytica, iron affects the growth, pathogenicity mechanisms, and expression of virulence genes. One of the proposed iron regulatory mechanisms is at the post-transcriptional level through an IRE/IRP-like (iron responsive element/iron regulatory protein) system. Recently, the expression of many putative giardial virulence factors in the free-iron levels has been reported in subsequent RNAseq experiments; however, the iron regulatory mechanism remains unknown. Thus, this work aimed to determine the effects of iron on the growth, gene expression, and presence of IRE-like structures in G. duodenalis. First, the parasite’s growth kinetics at different iron concentrations were studied, and the cell viability was determined. It was observed that the parasite can adapt to an iron range from 7.7 to 500 µM; however, in conditions without iron, it is unable to survive in the culture medium. Additionally, the iron modulation of three genes was determined by RT-PCR assays. The results suggested that Actin, glucosamine-6-phosphate deaminase, and cytochrome b5 mRNA were down-regulated by iron. To investigate the presence of IRE-like structures, in silico analyses were performed for different mRNAs from the Giardia genome database. The Zuker mfold v2.4 web server and theoretical analysis were used to predict the secondary structures of the 91 mRNAs analyzed. Interestingly, the iron-induced downregulation of the genes analyzed corresponds to the location of the stem–loop structures found in their UTR regions. In conclusion, iron modulates the growth and expression of specific genes, likely due to the presence of IRE-like structures in G. duodenalis mRNAs.

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Section: Discussionmentioning

confidence: 70%

Stem–Loop Structures in Iron-Regulated mRNAs of Giardia duodenalis

Plata-Guzmán

Arroyo

León-Sicairos

et al. 2023

IJERPH

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“…Iron is an essential trace-metal for all organisms and it is a well-known regulator of virulence genes in many pathogenic bacteria (Begg, 2019) but also in pathogenic protozoa, including Entamoeba histolytica, Trichomonas vaginalis, Trypanosoma, and Leishmania (Niu et al, 2016;Gastelum-Martínez et al, 2018;Paiva et al, 2018). This is because iron is an essential constituent of many proteins in the pathogens, including metabolic and antioxidant enzymes and virulence factors (Arroyo et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The observed effects of iron on the expression of a small set of HCMPs and the fact the iron is a well-known regulator of virulence in intestinal bacteria (Begg, 2019) and protozoa (Gastelum-Martínez et al, 2018) inspired us to study the effects of iron on the total Giardia transcriptome. RNA Sequencing was performed on trophozoites grown in media with different levels of free iron to assess global changes in gene expression.…”

Section: Giardia Responses To Iron Depletionmentioning

confidence: 99%

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

Peirasmaki

Ma’ayeh

et al. 2020

Front. Genet.

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Giardia intestinalis colonizes the upper small intestine of humans and animals, causing the diarrheal disease giardiasis. This unicellular eukaryotic parasite is not invasive but it attaches to the surface of small intestinal epithelial cells (IECs), disrupting the epithelial barrier. Here, we used an in vitro model of the parasite's interaction with host IECs (differentiated Caco-2 cells) and RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) in Giardia, which might relate to the establishment of infection and disease induction. Giardia trophozoites interacted with differentiated Caco-2 cells for 1.5, 3, and 4.5 h and at each time point, 61, 89, and 148 parasite genes were up-regulated more than twofold, whereas 209, 265, and 313 parasite genes were down-regulated more than twofold. The most abundant DEGs encode hypothetical proteins and members of the High Cysteine Membrane Protein (HCMP) family. Among the up-regulated genes we also observed proteins associated with proteolysis, cellular redox balance, as well as lipid and nucleic acid metabolic pathways. In contrast, genes encoding kinases, regulators of the cell cycle and arginine metabolism and cytoskeletal proteins were down-regulated. Immunofluorescence imaging of selected, up-regulated HCMPs, using C-terminal HA-tagging, showed localization to the plasma membrane and peripheral vesicles (PVs). The expression of the HCMPs was affected by histone acetylation and free iron-levels. In fact, the latter was shown to regulate the expression of many putative giardial virulence factors in subsequent RNAseq experiments. We suggest that the plasma membrane localized and differentially expressed HCMPs play important roles during Giardia-host cell interactions.

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“…Furthermore, if the accompanying bacterial flora is eliminated, the virulence of E. histolytica decreases rapidly; therefore, some strains that have been grown axenically for many years have lost their pathogenicity (Bos and Van de Griend, 1977; Costa et al ., 2006). Moreover, it has been suggested that nutritional modifications may alter the motility, and expression of the virulence factors for this parasite (Marie and Petri, 2014; Gastelum-Martínez et al ., 2018). The objective of the current study was to evaluate the impact of vitamin supplementation on the pathogenicity of E. histolytica grown axenically.…”

Section: Introductionmentioning

confidence: 99%

Vitamin supplementation increases the virulence ofEntamoeba histolyticagrown axenically

Lozano-Garza

Said‐Fernández

et al. 2020

Parasitology

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As a consequence of axenic growth and the elimination of accompanying bacterial flora, Entamoeba histolytica virulence decreases rapidly, and pathogenicity is lost. This paper evaluated the impact of vitamin supplementation on the pathogenicity of E. histolytica. Growth of E. histolytica trophozoites, cultured axenically in PEHPS (a Spanish acronym for the main ingredients – casein peptone, liver, pancreas extract and bovine serum) medium, with or without vitamins, exhibited a similar growth rate. However, the vitamin-enriched PEHPS preparations expressed 2.65 times more haemolytic activity (at 60 min: 98 vs 48%, P < 0.05), 2.5 times more phospholipase A2 activity at 150 min of incubation and generated more hepatic abscesses (88 vs 60%, P = 0.05) than the preparations without vitamins. The haemolytic and phospholipase A2 activity for the PEHPS − V preparations were restored following vitamin supplementation with A and D. These data highlight, for the first time, that vitamins and specifically vitamin A and D were essential for the recovery of amoebic virulence, lost through axenic growth.

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Iron-Modulated Virulence Factors of Entamoeba Histolytica

Cited by 12 publications

References 77 publications

Stem–Loop Structures in Iron-Regulated mRNAs of Giardia duodenalis

Stem–Loop Structures in Iron-Regulated mRNAs of Giardia duodenalis

High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions

Vitamin supplementation increases the virulence ofEntamoeba histolyticagrown axenically

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