Abstract
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.
Highlights
Blastocystis is a unicellular, genetically diverse protist, phylogenetically placed within the Stramenopiles [1], and it is the only member of this group associated with human pathological changes [2,3]
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 observed an inverse correlation between adhesiveness and drug resistance, suggesting that drug resistance might compromise the fitness of the parasite
Summary
Blastocystis is a unicellular, genetically diverse protist, phylogenetically placed within the Stramenopiles [1], and it is the only member of this group associated with human pathological changes [2,3]. It is a species complex comprising 17 subtypes (STs) at least 9 of which are found in humans [4,5]. Some select populations in developed countries may have much higher prevalence [7] It is frequently reported in human fecal samples from symptomatic patients as well as healthy individuals [8,9,10]. Patients immunocompromised due to HIV or cancer are susceptible to infections [15,16,17,18], suggesting that Blastocystis is an opportunistic pathogen
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