Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7
| العنوان: | Intra-Subtype Variation in Enteroadhesion Accounts for Differences in Epithelial Barrier Disruption and Is Associated with Metronidazole Resistance in Blastocystis Subtype-7 |
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| المؤلفون: | Haris Mirza, Zhaona Wu, Kevin S. W. Tan |
| المصدر: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 8, Iss 5, p e2885 (2014) |
| بيانات النشر: | Public Library of Science, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | lcsh:Arctic medicine. Tropical medicine, Cell Membrane Permeability, lcsh:RC955-962, Antiprotozoal Agents, Drug Resistance, Virulence, Drug resistance, Gastroenterology and Hepatology, Pathogenesis, Biology, Occludin, Pathology and Laboratory Medicine, Cell junction, Microbiology, Tight Junctions, Metronidazole, Medicine and Health Sciences, Parasitic Diseases, Cell Adhesion, Parasite hosting, Humans, Gastrointestinal Infections, Cell adhesion, Microbial Pathogens, Cell Proliferation, Blastocystis, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, Parasite Physiology, Biology and Life Sciences, lcsh:RA1-1270, biology.organism_classification, Intestinal epithelium, Infectious Diseases, Emerging Infectious Diseases, Blastocystis Hominis Infection, Medical Microbiology, Immunology, Host-Pathogen Interactions, Parasitology, Caco-2 Cells, Research Article |
| الوصف: | Blastocystis is an extracellular, enteric pathogen that induces intestinal disorders in a range of hosts including humans. Recent studies have identified potential parasite virulence factors in and host responses to this parasite; however, little is known about Blastocystis-host attachment, which is crucial for colonization and virulence of luminal stages. By utilizing 7 different strains of the parasite belonging to two clinically relevant subtypes ST-4 and ST-7, we investigated Blastocystis-enterocyte adhesion and its association with parasite-induced epithelial barrier disruption. We also suggest that drug resistance in ST-7 strains might result in fitness cost that manifested as impairment of parasite adhesion and, consequently, virulence. ST-7 parasites were generally highly adhesive to Caco-2 cells and preferred binding to intercellular junctions. These strains also induced disruption of ZO-1 and occludin tight junction proteins as well as increased dextran-FITC flux across epithelial monolayers. Interestingly, their adhesion was correlated with metronidazole (Mz) susceptibility. Mz resistant (Mzr) strains were found to be less pathogenic, owing to compromised adhesion. Moreover, tolerance of nitrosative stress was also reduced in the Mzr strains. In conclusion, the findings indicate that Blastocystis attaches to intestinal epithelium and leads to epithelial barrier dysfunction and that drug resistance might entail a fitness cost in parasite virulence by limiting entero-adhesiveness. This is the first study of the cellular basis for strain-to-strain variation in parasite pathogenicity. Intra- and inter-subtype variability in cytopathogenicity provides a possible explanation for the diverse clinical outcomes of Blastocystis infections. Author Summary Since it was first described more than a century ago, the question as to whether the protistan parasite Blastocystis causes disease or is a commensal of the human gut still remains unresolved. Strain- or subtype-dependent variability in Blastocystis pathogenicity has been proposed to contribute to this controversy. Currently, the factors determining this variation are unknown. For seven strains from two clinically relevant Blastocystis subtypes, we evaluated their ability to adhere to human intestinal epithelium and to disturb barrier function. We showed that the more adhesive strains exhibited greater pathogenicity. We also observed an inverse correlation between adhesiveness and drug resistance, suggesting that drug resistance might compromise the fitness of the parasite. This is the first study highlighting the important role of adhesion in Blastocystis pathogenesis. We conclude that the extensive variation in Blastocystis pathogenicity is a plausible factor contributing to the disparate outcomes of Blastocystis infections. |
| اللغة: | English |
| تدمد: | 1935-2735 1935-2727 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c76d748810e61c780f8e52b2b8a01676 http://europepmc.org/articles/PMC4031124 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c76d748810e61c780f8e52b2b8a01676 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19352735 19352727 |
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