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

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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 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.

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