Molecule Information

General Information of the Molecule (ID: Mol04278)

Name	Drug/Homo sapiens transporter 1 (DMT1/SLC11A2) ,Homo sapiens
Synonyms	Drug/Homo sapiens transporter 1 (DMT1/SLC11A2) Click to Show/Hide
Molecule Type	Protein
*Click to Show/Hide the Complete Species Lineage*
Kingdom: Metazoa Phylum: Chordata Class: Mammalia Order: Primates Family: Hominidae Genus: Homo Species: Homo sapiens

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

Click to Show/Hide the Full List of Drugs

Quinine

Click to Show/Hide

Drug Resistance Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)			Click to Show/Hide
Disease Class: Malaria [ICD-11: 1F45.0]				[1]
Resistant Disease	Malaria [ICD-11: 1F45.0]			Disease Info
Resistant Drug	Quinine			Drug Info
Molecule Alteration	Mutations		Y107N+S129L
Experimental Note	Revealed Based on the Cell Line Data
In Vitro Model	Human red blood cells	Blood	Homo sapiens (Human)	N.A.
In Vivo Model	Human liver-chimeric mouse model			Mus musculus
Experiment for Molecule Alteration	Genetic cross assay; Bulk segregant analysis; Progeny cloning assay
Experiment for Drug Resistance	Gene editing
Mechanism Description	For QN, resistance mapped to a dominant chromosome 7 peak centered 295 kb downstream of pfcrt, with pfcrt showing a smaller peak. We identified the drug/metabolite transporter 1 (DMT1) as the top chromosome 7 candidate due to its structural similarity to PfCRT and proximity to the peak. Deleting DMT1 in QN-resistant Cam3.II parasites significantly sensitized the parasite to QN but not to the other drugs tested, suggesting that DMT1 mediates QN response specifically. We localized DMT1 to structures associated with vesicular trafficking, as well as the parasitophorous vacuolar membrane, lipid bodies, and the digestive vacuole. We also observed that mutant DMT1 transports more QN than the wild-type isoform in vitro. Gene editing confirmed an additional role for mutant PfCRT in mediating QN resistance.

References

Ref 1	Plasmodium falciparum quinine resistance is multifactorial and includes a role for the drug/metabolite transporters PfCRT and DMT1. bioRxiv [Preprint]. 2025 Apr 11:2024.09.27.615529.