Changes in beta-giardin sequence of Giardia intestinalis sensitive and resistant to albendazole strains.
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.
Jiménez-Cardoso
Enedina
E
Hospital Infantil de México Federico Gómez, Delegación Cuauhtémoc, México D.F., México. enedina@servidor.unam.mx
Eligio-García
Leticia
L
Cortés-Campos
Adrián
A
Flores-Luna
Andrés
A
Valencia-Mayoral
Pedro
P
Lozada-Chávez
Irma
I
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
D000981:Antiprotozoal Agents; D003598:Cytoskeletal Proteins; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C038207:giardin protein, Giardia lamblia; D015766:Albendazole