Changes in β-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.

Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series

“…The high levels of corticosteroids used to prevent complications due to severe CSF inflammation may also turn-off key immunological components crucial for the parasite destruction. Finally, although resistance of cysticerci to ABZ in humans has never been reported, it may occur as it has been observed in other related parasites [13-15]. …”

Understanding drug resistance in human intestinal protozoa

“…Escobedo et al 2008 with a non-resistant one is used to elucidate potential drug targets (Paz-Maldonado et al 2013). Sequence alignments of the β giardin gene amplified from albendazole-sensitive and albendazole-resistant strains of Giardia revealed that resistance is accompanied by several amino acid mutations which result in altered protein folding in the three-dimensional structure of β-giardin, one of the cytoskeletal proteins (Jiménez-Cardoso et al 2009). The mutation in the β-tubulin gene which has been linked to benzimidazole resistance in nematode parasites of animals (Ghisi et al 2007) was not detected in albendazole-resistant Giardia (Argüello- ).…”

Gene mutations in parasitic diseases Part II: Parasite gene mutations

“…This was attributed to evident major chromosome rearrangements indicating differences in the cytoskeleton between sensitive and resistant lines [166] . On the other hand, Jiménez-Cardoso et al [167] found several mutations in the β-giardin gene in both albendazoleresistant and recovered-sensitive G. lamblia strains indicating that resistance to albendazole is not necessarily caused by mutations in the β-giardin gene of G. lamblia.…”

“…American investigators applied real time PCR assays to screen development of benzimidazoles resistance in Ancylostoma caninuminfected dogs. They found elevated levels of β-tubulin isotype-1 gene polymorphisms at codon positions 167,198 and 200 in hookworm resistant strains [198] . β-tubulin gene isoform 2 was also incriminated in benzimidazole resistant Echinococcus granulosus strains in post-surgical treatment of hydatid cyst in a study conducted in India [199] .…”