Open AccessA Metronidazole-Resistant Isolate of Blastocystis spp. Is Susceptible to Nitric Oxide and Downregulates Intestinal Epithelial Inducible Nitric Oxide Synthase by a Novel Parasite Survival Mechanism
Author(s) -
Haris Mirza,
WU Zong-hua,
Fahad Kidwai,
Kevin S. W. Tan
Publication year - 2011
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.05632-11
Subject(s) - blastocystis , biology , microbiology and biotechnology , nitric oxide synthase , nitric oxide , pathogenesis , intestinal epithelium , metronidazole , diarrhea , immunology , epithelium , pathology , feces , antibiotics , medicine , genetics , endocrinology
Blastocystis , one of the most common parasites colonizing the human intestine, is an extracellular, noninvasive, luminal protozoan with controversial pathogenesis.Blastocystis infections can be asymptomatic or cause intestinal symptoms of vomiting, diarrhea, and abdominal pain. Although chronic infections are frequently reported,Blastocystis infections have also been reported to be self-limiting in immunocompetent patients. Characterizing the host innate response toBlastocystis would lead to a better understanding of the parasite's pathogenesis. Intestinal epithelial cells produce nitric oxide (NO), primarily on the apical side, in order to target luminal pathogens. In this study, we show that NO production by intestinal cells may be a host defense mechanism againstBlastocystis . Two clinically relevant isolates ofBlastocystis , ST-7 (B) and ST-4 (WR-1), were found to be susceptible to a range of NO donors. ST-7 (B), a metronidazole-resistant isolate, was found to be more sensitive to nitrosative stress. Using the Caco-2 model of human intestinal epithelium,Blastocystis ST-7 (B) but not ST-4 (WR-1) exhibited dose-dependent inhibition of Caco-2 NO production, and this was associated with downregulation of inducible nitric oxide synthase (iNOS). Despite its higher susceptibility to NO,Blastocystis ST-7 (B) may have evolved unique strategies to evade this potential host defense by depressing host NO production. This is the first study to highlight a strain-to-strain variation in the ability ofBlastocystis to evade the host antiparasitic NO response.