Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum
Table 4
List of the plausible mutations that may occur in pfcrt within the regions 72–76 along with their geographic distribution, effect on channel physiochemical properties, and their impact on the phenotype of the parasite toward chloroquine resistance.
Mutation
Geographic distribution
Effect on channel negativity
Effect on side chain volume
Effect on the channel lipophilicity
Overall effect on chloroquine resistance and VPL induced reversal of CQ resistance
C72S
CQ resistant strains of the new world
High increase
Decrease
Imparts for non VPL reversible CQ resistance
N74I
Old World CQ resistant strains
High increase
Increase
Imparts for VPL reversible CQ resistance
N75D
Cambodian CQ resistant strains
Increase
Decrease
Imparts for higher CQR without affecting VPL binding
N75E
Old World CQ resistant strains
Increase
No effect
Imparts for higher CQR without affecting VPL binding
K76N
Long term exposure of 106/I strain to CQ
Increase
Imparts for VPL reversible CQR with IC50 of about 12-folds that of 106/I. On the other hand, it imparts for higher MQ, HF, LM, and DHA activity
K76I
Long term exposure of 106/I strain to CQ
Increase
Imparts for higher CQR with IC50 of about 12-folds that of 106/I. On the other hand, it imparts for higher MQ, HF, LM, and DHA activity
