title: Blastocystis Isolate B Exhibits Multiple Modes of Resistance against Antimicrobial Peptide LL-37.
abstract: Blastocystis is one of the most common eukaryotic organisms found in humans and many types of animals. Several reports have identified its role in gastrointestinal disorders, although its pathogenicity is yet to be clarified. Blastocystis is transmitted via the fecal-to-oral route and colonizes the large intestines. Epithelial cells lining the intestine secrete antimicrobial peptides (AMPs), including beta-defensins and cathelicidin, as a response to infection. This study explores the effects of host colonic antimicrobial peptides, particularly LL-37, a fragment of cathelicidin, on different Blastocystis subtypes. Blastocystis is composed of several subtypes that have genetic, metabolic, and biological differences. These subtypes also have various outcomes in terms of drug treatment and immune response. In this study, Blastocystis isolates from three different subtypes were found to induce intestinal epithelial cells to secrete LL-37. We also show that among the antimicrobial peptides tested, only LL-37 has broad activity on all the subtypes. LL-37 causes membrane disruption and causes Blastocystis to change shape. Blastocystis subtype 7 (ST7), however, showed relative resistance to LL-37. An isolate, ST7 isolate B (ST7-B), from this subtype releases proteases that can degrade the peptide. It also makes the environment acidic, which causes attenuation of LL-37 activity. The Blastocystis ST7-B isolate was also observed to have a thicker surface coat, which may protect the parasite from direct killing by LL-37. This study determined the effects of LL-37 on different Blastocystis isolates and indicates that AMPs have significant roles in Blastocystis infections.
authors.affiliation: Laboratory of Cellular and Molecular Parasitology, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: John Anthony
authors.initials: JA
authors.lastname: Yason
authors.affiliation: Laboratory of Cellular and Molecular Parasitology, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Sitara Swarna Rao
authors.initials: SSR
authors.lastname: Ajjampur
authors.affiliation: Laboratory of Cellular and Molecular Parasitology, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore kevin_tan@nuhs.edu.sg.
authors.forename: Kevin Shyong Wei
authors.initials: KSW
authors.lastname: Tan
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides; D016844:Blastocystis / Q000187:drug effects* / Q000648:ultrastructure; D016776:Blastocystis Infections / Q000378:metabolism / Q000469:parasitology*; D054804:Cathelicidins / Q000096:biosynthesis / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D004195:Disease Models, Animal; D004351:Drug Resistance; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D021261:Parasitic Sensitivity Tests
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins