Giardia intestinalis extracellular vesicles induce changes in gene expression in human intestinal epithelial cells in vitro

Experimental Parasitology, Journal Year: 2024, Volume and Issue: 262, P. 108788 - 108788

Published: May 15, 2024

Language: Английский

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Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(5), P. e1011372 - e1011372

Published: May 4, 2023

Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause diarrhoeal disease giardiasis in humans and animals, but at least half are asymptomatic. However, molecular underpinnings these different outcomes infection still poorly defined. Here, we studied early transcriptional response to G. trophozoites, disease-causing life-cycle stage, human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned media that maximise fitness triggered only neglectable inflammatory transcription IECs during first hours co-incubation. By sharp contrast, "non-fit" or lysed trophozoites induced vigorous IEC response, including high up-regulation many cytokines chemokines. Furthermore, "fit" could even suppress stimulatory effect mixed infections, suggesting active suppression response. dual-species RNA-sequencing, defined gene expression programs associated with differential infection. Taken together, our results inform on how can lead such highly variable effects host, pinpoints trophozoite as key determinant this common parasite.

Language: Английский

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Protozoa-Derived Extracellular Vesicles on Intercellular Communication with Special Emphasis on Giardia lamblia

Microorganisms, Journal Year: 2022, Volume and Issue: 10(12), P. 2422 - 2422

Published: Dec. 7, 2022

Parasitic diseases are an important worldwide problem threatening human health and affect millions of people. Acute diarrhea, intestinal bleeding, malabsorption nutrients nutritional deficiency some the issues related to parasitic infections. Parasites experts in subvert host immune system through different kinds mechanisms. There evidences that extracellular vesicles (EVs) have role dissemination disease modulating system. Released by almost all types cells, these nanovesicles a natural secretory product containing multiple components interest. The EVs classified as apoptotic bodies, microvesicles, exosomes, ectosomes, microparticles, according their physical characteristics, biochemical composition cell origin. Interestingly, play intercellular communication between parasites well with cells. Concerning Giardia lamblia, it is known this parasite release during life cycle modulate growth adherence host. Here we review recently updates on protozoa EVs, particular emphasis released flagellate G. lamblia cellular its potential for future applications vaccine, therapeutic agent, drug delivery diagnostic or prognostic biomarker.

Language: Английский

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Assessment of Drug Activities against Giardia Using Hyperspectral Raman Microscopy

Pathogens, Journal Year: 2024, Volume and Issue: 13(5), P. 358 - 358

Published: April 27, 2024

This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects by inducing extracellular vesicle releases toxic iron intermediates modified triple-bond moieties, oseltamivir (OSM) alters phenylalanine lipid structures. Modifications heme protein environment transformation from ferric ferrous observed both drug treatments are more notable MTZ. Different contents amounts excretion detected 24 h or 48 with MTZ incubation. At a shorter exposure, altered proteins, glycogen, phospholipids dominate. Agglomerates transformed complexes proteins multiple-bond moieties prevail at treatment. No such present case OSM usage. Drug incorporations into their impact on plasma membrane dynamics raft confirmed confocal fluorescence reveal destructive extent OSM, corroborating results. provides broader understanding multifaceted factors mechanisms responsible giardiasis treatment resistance enabling label-free, simultaneous monitoring changes cellular molecular levels.

Language: Английский

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Synthetic Oseltamivir Analogs Targeting Lipid Rafts and Extracellular Vesicles in Giardia: Identification of Potential New Line of Therapeutics Against Giardiasis

Published: Jan. 1, 2024

Extracellular vesicles (EVs) are nanoscale lipid entities released by various cell types, including parasitic cells.Giardialamblia is a protozoan parasite responsible for enteric disease globally. Because it non-invasive parasite, the mechanisms which causes infection unclear. Recent evidence suggests that microvesicles (MVs) and exosomes (EXOs) Giardia carry virulent factors paralyze host's immune defenses produce infections in gut. We reported earlier oseltamivir (Osm, Tamiflu®), an anti-viral agent, inhibits attachment of trophozoites to intestinal epithelial cells cyst production culture. Osm also disassembles rafts (LRs) biogenesis EVs Giardia. In current study, we synthesized forty-three analogs with derivatization phosphate. These compounds were tested on giardial growth, Caco-2 cells, production, LR assembly, EV biogenesis. Of these, four analogs, i.e., 3b, 2c, 11i, 11d, found be active reducing growth (IC50 ~30-50 µM), (~65-102 encystation ~40-50 assembly MVs EXOs (~20 µM). Some demonstrated preferential activities EXOs, suggesting vesicle subtypes structurally functionally different. propose these synthetic should effective treating giardiasis alone or combination other anti-giardial agents because target previously unexploited pathway, they potentially useful treatment drug-resistant giardiasis.

Language: Английский

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Extracellular vesicles release from protozoa parasite and animal model

Current topics in membranes, Journal Year: 2024, Volume and Issue: unknown, P. 85 - 106

Published: Jan. 1, 2024

Language: Английский

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Synthesis and evaluation of anti-Giardia activity of oseltamivir analogs

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: unknown, P. 130035 - 130035

Published: Nov. 1, 2024

Language: Английский

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