Intra-subtype variation in enteroadhesion accounts for differences in epithelial barrier disruption and is associated with metronidazole resistance in Blastocystis subtype-7.

作者: Zhaona Wu , Haris Mirza , Kevin Shyong Wei Tan

DOI: 10.1371/JOURNAL.PNTD.0002885

关键词:

摘要: 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 and host responses to this parasite; however, little known about Blastocystis-host attachment, which crucial for colonization luminal stages. By utilizing 7 different strains the belonging two clinically relevant subtypes ST-4 ST-7, we investigated Blastocystis-enterocyte adhesion its association with parasite-induced epithelial barrier disruption. We also suggest drug resistance ST-7 might result fitness cost manifested as impairment and, consequently, virulence. parasites were generally highly adhesive Caco-2 cells preferred binding intercellular junctions. These induced disruption ZO-1 occludin tight junction proteins well increased dextran-FITC flux across monolayers. Interestingly, their was correlated metronidazole (Mz) susceptibility. Mz resistant (Mzr) found be less pathogenic, owing compromised adhesion. Moreover, tolerance nitrosative stress reduced Mzr strains. In conclusion, findings indicate attaches epithelium leads dysfunction entail by limiting entero-adhesiveness. This first study cellular basis strain-to-strain variation pathogenicity. Intra- inter-subtype variability cytopathogenicity provides possible explanation diverse clinical outcomes infections.

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