Changes in β-giardin sequence of Giardia intestinalis sensitive and resistant to albendazole strains

• Published in: Parasitology research (1987) 2009-07, Vol.105 (1), p.25-33
• Main Authors: Jiménez-Cardoso, Enedina, Eligio-García, Leticia, Cortés-Campos, Adrián, Flores-Luna, Andrés, Valencia-Mayoral, Pedro, Lozada-Chávez, Irma
• Format: Article
• Language: English
• Subjects: albendazole; Albendazole - pharmacology; Amino Acid Sequence; Animals; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cytoskeletal Proteins - genetics; DNA, Protozoan - chemistry; DNA, Protozoan - genetics; Drug Resistance; Fundamental and applied biological sciences. Psychology; General aspects; General aspects and techniques. Study of several systematic groups. Models; genes; Giardia lamblia; Giardia lamblia - drug effects; Giardia lamblia - genetics; giardin protein; Immunology; Inhibitory Concentration 50; Invertebrates; Medical Microbiology; Microbiology; Models, Molecular; Molecular Sequence Data; mutation; Mutation, Missense; Original Paper; Parasitic Sensitivity Tests; polymerase chain reaction; Polymorphism, Genetic; Protozoan Proteins - genetics; sequence analysis; Sequence Analysis, DNA; Sequence Homology, Amino Acid
• ISSN: 0932-0113; 1432-1955
• DOI: 10.1007/s00436-009-1363-7

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 β-giardin gene of G. intestinalis strains: sensitive, resistant, or recovered-resistance to albendazole. The β-giardin gene was amplified by nested polymerase chain reaction. The IC₅₀ values varied from 0.29 to 0.38 μg/mL for strains sensitive to albendazole. For resistant strains, the IC₅₀ range was 1.31-2.12 μg/mL. Recovered-sensitivity albendazole strains' IC₅₀ values were 0.33-0.49 μg/mL, and for strains with recovered-resistance, the IC₅₀ was 1.42-2.74 μg/mL. β-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 β-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 β-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 β-giardin gene of G. intestinalis.