title: Activity of benzimidazoles against Dientamoeba fragilis (Trichomonadida, Monocercomonadidae) in vitro and correlation of beta-tubulin sequences as an indicator of resistance.
abstract: Recently, Dientamoeba fragilis has emerged as a significant and common enteropathogen. The majority of patients with dientamoebiasis present with gastrointestinal complaints and chronic symptoms are common. Numerous studies have successfully demonstrated parasite clearance, coupled with complete resolution of clinical symptoms following treatment with various antiparasitic compounds. Despite this, there is very little in vitro susceptibility data available for the organism. Benzimidazoles are a class of antiparasitic drugs that are commonly used for the treatment of protozoan and helminthic infections. Susceptibility testing was undertaken on four D. fragilis clinical isolates against the following benzimidazoles: albendazole, flubendazole, mebendazole, nocodazole, triclabendazole and thiabendazole. The activities of the antiprotozoal compounds at concentrations ranging from 2 μg/mL to 500 μg/mL were determined via cell counts of D. fragilis grown in xenic culture. All tested drugs showed no efficacy. The beta-tubulin transcript was sequenced from two of the D. fragilis isolates and amino acid sequences predicted a susceptibility to benzimidazoles. This is the first study to report susceptibility profiles for benzimidazoles against D. fragilis, all of which were not active against the organism. This study also found that beta-tubulin sequences cannot be used as a reliable marker for resistance of benzimidazoles in D. fragilis.
authors.affiliation: Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia - University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway 2007, Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Stark
authors.affiliation: University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway 2007, Australia - University of Technology Sydney, iThree Institute, Broadway 2007, Australia.
authors.forename: Joel L N
authors.initials: JL
authors.lastname: Barratt
authors.affiliation: Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia - University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway 2007, Australia.
authors.forename: Tamalee
authors.initials: T
authors.lastname: Roberts
authors.affiliation: Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia - University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway 2007, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Marriott
authors.affiliation: Division of Microbiology, SydPath, St. Vincent's Hospital, Darlinghurst, NSW 2010, Australia - University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway 2007, Australia.
authors.forename: John T
authors.initials: JT
authors.lastname: Harkness
authors.affiliation: University of Technology Sydney, School of Medical and Molecular Biosciences, Broadway 2007, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Ellis
mesh_terms: D000595:Amino Acid Sequence; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D016384:Consensus Sequence; D004029:Dientamoeba / Q000187:drug effects* / Q000235:genetics; D004351:Drug Resistance; D005838:Genotype; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics*; D016053:RNA, Protozoan / Q000096:biosynthesis / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D059467:Transcriptome; D014404:Tubulin / Q000235:genetics*
chemical_list: D000981:Antiprotozoal Agents; D001562:Benzimidazoles; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D014404:Tubulin