Entamoeba histolytica EhCP112 Dislocates and Degrades Claudin-1 and Claudin-2 at Tight Junctions of the Intestinal Epithelium

Cuellar, Patricia; Hernández-Nava, Elizabeth; Garcı́a-Rivera, Guillermina; Chávez‐Munguía, Bibiana; Schnoor, Michael; Betanzos, Abigail; Orozco, Esther

doi:10.3389/fcimb.2017.00372

Cited by 33 publications

(44 citation statements)

References 60 publications

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“…All these processes are performed with the active participation of lipids (Espinosa-Cantellano and Martinez-Palomo, 2000;Byekova et al, 2010;Das and Nozaki, 2018). Trophozoites degrade the mucus layer by the secretion of glycosidases and cysteine proteases (Espinosa-Cantellano and Martinez-Palomo, 2000;Cuellar et al, 2017). Thanks its lipid composition, amebic membranes are resistant to the lytic compounds of the parasite (Andrä et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…The EhCPADH complex, formed by a cysteine protease (EhCP112) and an adhesin (EhADH), is also involved in adherence to and destruction of the epithelium (Cuellar et al, 2017;Hernández-Nava et al, 2017). Through the cysteine protease, this complex destroys the mucus layer; and by the adhesin, it enhances the trophozoites adherence to the epithelium.…”

Section: Introductionmentioning

confidence: 99%

“…Through the cysteine protease, this complex destroys the mucus layer; and by the adhesin, it enhances the trophozoites adherence to the epithelium. Once adhered to the cells, EhCPADH opens the cellular junctions, provoking the epithelium destruction (Cuellar et al, 2017;Hernández-Nava et al, 2017). EhADH binds to cholesterol and the phospholipid lysobisphosphatidic acid (LBPA) (Bolaños et al, 2016;Castellanos-Castro et al, 2016), but the participation of lipid rafts in this protein functions has not been studied yet…”

Section: Introductionmentioning

confidence: 99%

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Lipids in Entamoeba histolytica: Host-Dependence and Virulence Factors

Castellanos-Castro

Bolaños

Orozco

2020

Front. Cell. Infect. Microbiol.

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Lipids are essential players in parasites pathogenesis. In particular, the highly phagocytic trophozoites of Entamoeba histolytica, the causative agent of amoebiasis, exhibit a dynamic membrane fusion and fission, in which lipids strongly participate; particularly during the overstated motility of the parasite to reach and attack the epithelia and ingest target cells. Synthesis and metabolism of lipids in this protozoan present remarkable difference with those performed by other eukaryotes. Here, we reviewed the current knowledge on lipids in E. histolytica. Trophozoites synthesize phosphatidylcholine and phosphatidylethanolamine by the Kennedy pathway; and sphingolipids, phosphatidylserine, and phosphatidylinositol, by processes similar to those used by other eukaryotes. However, trophozoites lack enzymes for cholesterol and fatty acids synthesis, which are scavenged from the host or culture medium by specific mechanisms. Cholesterol, a fundamental molecule for the expression of virulence, is transported from the medium into the trophozoites by EhNPC1 and EhNPC2 proteins. Inside cells, lipids are distributed by different pathways, including by the participation of the endosomal sorting complex required for transport (ESCRT), involved in vesicle fusion and fission. Cholesterol interacts with the phospholipid lysobisphosphatidic acid (LBPA) and EhADH, an ALIX family protein, also involved in phagocytosis. In this review, we summarize the known information on phospholipids synthesis and cholesterol transport as well as their metabolic pathways in E. histolytica; highlighting the mechanisms used by trophozoites to dispose lipids involved in the virulence processes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipids in Entamoeba histolytica: Host-Dependence and Virulence Factors

Castellanos-Castro

Bolaños

Orozco

2020

Front. Cell. Infect. Microbiol.

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“…The results showed that the trophozoites and their CM produced a substantial cytopathic effect and an important decrease of TEER in the RBMEC culture. Previous reports showed that the cytopathic damage produced by A. castellanii, E. histolytica, Toxoplasma gondii, and Giardia duodenalis in HBMEC and MDCK cells, was the result of the action of their proteases (Betanzos et al 2013;Briceno et al 2016;Cuellar et al 2017;Halliez et al 2016;Khan and Siddiqui 2009;Shibayama et al 2013). To evaluate the damage produced by the amoebic proteases, we preincubated the trophozoites and their CM with E-64 or Aprotinin and observed that the cysteine proteases inhibitor but not the serine proteases exerted a protective effect on the endothelial monolayer.…”

Section: Discussionmentioning

confidence: 96%

An In Vitro Model of the Blood–Brain Barrier: Naegleria fowleri Affects the Tight Junction Proteins and Activates the Microvascular Endothelial Cells

Coronado-Velázquez

Betanzos

Serrano-Luna

et al. 2018

J Eukaryotic Microbiology

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Naegleria fowleri causes a fatal disease known as primary amoebic meningoencephalitis. This condition is characterized by an acute inflammation that originates from the free passage of peripheral blood cells to the central nervous system through the alteration of the blood-brain barrier. In this work, we established models of the infection in rats and in a primary culture of endothelial cells from rat brains with the aim of evaluating the activation and the alterations of these cells by N. fowleri. We proved that the rat develops the infection similar to the mouse model. We also found that amoebic cysteine proteases produced by the trophozoites and the conditioned medium induced cytopathic effect in the endothelial cells. In addition, N. fowleri can decrease the transendothelial electrical resistance by triggering the destabilization of the tight junction proteins claudin-5, occludin, and ZO-1 in a time-dependent manner. Furthermore, N. fowleri induced the expression of VCAM-1 and ICAM-1 and the production of IL-8, IL-1β, TNF-α, and IL-6 as well as nitric oxide. We conclude that N. fowleri damaged the blood-brain barrier model by disrupting the intercellular junctions and induced the presence of inflammatory mediators by allowing the access of inflammatory cells to the olfactory bulbs.

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“…EhCPADH, EhADH, and EhCP112 are secreted during trophozoite attack (Ocádiz et al, 2005 ; Bolaños et al, 2016 ). Moreover, an EhCP112 recombinant protein drops TEER of epithelial cells, and dislocates and degrades junctional molecules, including claudin-1, claudin-2, β-catenin, E-cadherin, desmoplakin-I/II and desmoglein-2 (Cuellar et al, 2017 ; Hernández-Nava et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Epithelial Cells Expressing EhADH, An Entamoeba histolytica Adhesin, Exhibit Increased Tight Junction Proteins

Betanzos

Zanatta

Bañuelos

et al. 2018

Front. Cell. Infect. Microbiol.

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In Entamoeba histolytica, the EhADH adhesin together with the EhCP112 cysteine protease, form a 124 kDa complex named EhCPADH. This complex participates in trophozoite adherence, phagocytosis and cytolysis of target cells. EhCPADH and EhCP112 are both involved on epithelium damage, by opening tight junctions (TJ) and reaching other intercellular junctions. EhADH is a scaffold protein belonging to the ALIX family that contains a Bro1 domain, expresses at plasma membrane, endosomes and cytoplasm of trophozoites, and is also secreted to the medium. Contribution of EhADH to TJ opening still remains unknown. In this paper, to elucidate the role of EhADH on epithelium injury, we followed two strategies: producing a recombinant protein (rEhADH) and transfecting the ehadh gene in MDCK cells. Results from the first strategy revealed that rEhADH reached the intercellular space of epithelial cells and co-localized with claudin-1 and occludin at TJ region; later, rEhADH was mainly internalized by clathrin-coated vesicles. In the second strategy, MDCK cells expressing EhADH (MDCK-EhADH) showed the adhesin at plasma membrane. In addition, MDCK-EHADH cells exhibited adhesive features, producing epithelial aggregation and adherence to erythrocytes, as described in trophozoites. Surprisingly, the adhesin expression produced an increase of claudin-1, occludin, ZO-1 and ZO-2 at TJ, and also the transepithelial electric resistance (TEER), which is a measure of TJ gate function. Moreover, MDCK-EhADH cells resulted more susceptible to trophozoites attack, as showed by TEER and cytopathic experiments. Overall, our results indicated that EhADH disturbed TJ from the extracellular space and also intracellularly, suggesting that EhADH affects by itself TJ proteins, and possibly synergizes the action of other parasite molecules during epithelial invasion.

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Entamoeba histolytica EhCP112 Dislocates and Degrades Claudin-1 and Claudin-2 at Tight Junctions of the Intestinal Epithelium

Cited by 33 publications

References 60 publications

Lipids in Entamoeba histolytica: Host-Dependence and Virulence Factors

Lipids in Entamoeba histolytica: Host-Dependence and Virulence Factors

An In Vitro Model of the Blood–Brain Barrier: Naegleria fowleri Affects the Tight Junction Proteins and Activates the Microvascular Endothelial Cells

Epithelial Cells Expressing EhADH, An Entamoeba histolytica Adhesin, Exhibit Increased Tight Junction Proteins

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