title: Changes in beta-giardin sequence of Giardia intestinalis sensitive and resistant to albendazole strains.
abstract: Giardia intestinalis can develop resistance to albendazole, although the molecular mechanism is not understood. The aim of this study was to investigate the differences and permanent mutation in the beta-giardin gene of G. intestinalis strains: sensitive, resistant, or recovered-resistance to albendazole. The beta-giardin gene was amplified by nested polymerase chain reaction. The IC(50) values varied from 0.29 to 0.38 microg/mL for strains sensitive to albendazole. For resistant strains, the IC(50) range was 1.31-2.12 microg/mL. Recovered-sensitivity albendazole strains' IC(50) values were 0.33-0.49 microg/mL, and for strains with recovered-resistance, the IC(50) was 1.42-2.74 microg/mL. beta-giardin amplicon (720 bp) was sequenced and analysis sequence revealed several amino acid mutations from resistant and recovered-sensitive strains of G. intestinalis. Most of the mutations were located in the ROD domain of beta-giardin with a change from the sequence "TIARERA" in sensitive strains instead "IDRPRE" in resistant strains. A comparative sequence analysis in resistant, recovered-sensitive, and resistant-recovered strains revealed permanent mutation. This is the first report of combinatorial serine-proline-arginine repeats in the ROD domain of beta-giardin, whereas such repeats have been reported previously in the HEAD domain of SF-assemblin proteins. This is the first time that the resistance to albendazole correlates with genetics but it is not necessarily caused by mutations in the beta-giardin gene of G. intestinalis.
authors.affiliation: Hospital Infantil de México Federico Gómez, Delegación Cuauhtémoc, México D.F., México. enedina@servidor.unam.mx
authors.forename: Enedina
authors.initials: E
authors.lastname: Jiménez-Cardoso
authors.forename: Leticia
authors.initials: L
authors.lastname: Eligio-García
authors.forename: Adrián
authors.initials: A
authors.lastname: Cortés-Campos
authors.forename: Andrés
authors.initials: A
authors.lastname: Flores-Luna
authors.forename: Pedro
authors.initials: P
authors.lastname: Valencia-Mayoral
authors.forename: Irma
authors.initials: I
authors.lastname: Lozada-Chávez
mesh_terms: D015766:Albendazole / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D016829:Giardia lamblia / Q000187:drug effects / Q000235:genetics*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D021261:Parasitic Sensitivity Tests; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D000981:Antiprotozoal Agents; D003598:Cytoskeletal Proteins; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C038207:giardin protein, Giardia lamblia; D015766:Albendazole