Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum
Table 5
List of some famous mutations in pfcrt in foci far from 72 to 76 regions 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
H97Q
Only in TM90-6CB, the Thai CQ resistant strain
Increase
No effect
Imparts for higher CQ resistance without affecting VPL binding
A220S
All CQ resistant strains
Increase
Decrease
Impart for non-VPL reversible CQ resistance
Q271E
Old World CQ resistant strains and the CQ susceptible strains derived from KH1 strain
Increase
Imparts for higher CQ resistance without affecting VPL binding
N326S
Old World CQ resistant strains and the CQ susceptible strains derived from KH1 strain
Increase
Imparts for reversibility of CQ resistance by VPL
I356T
Some CQ resistant strains in Southeast Asia, namely, Dd2, BC7, BC22, KS28, and 738
Increase
Decrease
Decrease
Impart for non-VPL reversible CQ resistance (it explains why VPL reversibility is higher in K1 rather than in Dd2)
I356L
New World CQ resistant strains
Little increase
Little increase
Imparts for higher CQ resistance and VPL induced reversibility of CQ resistance
R371
Old World CQ resistant strains and the CQ susceptible strains derived from KH1 strain
Increase
Impart for VPL induced reversibility of CQ resistance