Molecule Information

General Information of the Molecule (ID: Mol02106)

• Name: High-affinity pentamidine transporter (HAPT1) ,Trypanosoma
• Synonyms: HAPT1
• Molecule Type: Protein
• Gene Name: HAPT1

Kingdom: N.A.
Phylum: Euglenozoa
Class: Kinetoplastea
Order: Trypanosomatida
Family: Trypanosomatidae
Genus: .
Species: Trypanosoma

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Pentamidine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: African trypanosomiasis [1]

• Resistant Disease: African trypanosomiasis [ICD-11: 1F51.0]
• Resistant Drug: Pentamidine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Trypanosoma brucei strain; 5691
• Mechanism Description: While a high level of resistance to diminazene was observed, the resistance factor for pentamidine and the melaminophenyl arsenicals were only two to threefold, significantly less than the arsenical-pentamidine cross-resistant strains generated in the laboratory. Thus, it was clear that at least one additional transporter must contribute to the cross-resistance phenotype. The prime candidate was the high-affinity pentamidine transporter (HAPT1), an activity recorded in bloodstream-form T. brucei using low nanomolar concentrations of [3H]-pentamidine. Melarsoprol also appears to be a substrate for HAPT1 and selection for increased resistance to pentamidine or melarsoprol in Tbat1 null cells led to specific loss of HAPT1 activity.

References

• Ref 1: Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story .Trends Parasitol. 2013 Mar;29(3):110-8. doi: 10.1016/j.pt.2012.12.005. Epub 2013 Jan 30. 10.1016/j.pt.2012.12.005