However, switching from sialic acid dependent to independent invasion is reversible and depends on the parasite ligand used [ 3, 5].
Whereas, APF and ellagic acid dependent antimicrobial activity suggests potential inhibition by membrane-transport and/or electron transport disruption.
These include both sialic acid dependent and independent parasite molecules.
Like EBA-175, PfRH1 has been shown to be a major ligand for sialic acid dependent invasion as all sialic acid dependent clones express high levels of PfRH1 [21].
PfRH1 has been shown to bind erythrocytes in a sialic acid dependent, trypsin resistant, chymotrypsin resistant manner [11], [21], [22].
Thus the binding phenotype of the 80 kDa smaller processed fragment of PfRH2a/b was sialic acid dependent, trypsin resistant and chymotrypsin sensitive.
The sialic acid dependent lines such as Dd2, MCamp and FCR3 express higher levels of PfRH1 and low levels of PfRH2a/2b [18], [21], [21].
This was further confirmed in invasion assays with the Dd2 parasite clone that invades erythrocytes only through sialic acid dependent pathways.
On the other hand, the smaller 80 kDa processed fragment of PfRH2a/b was observed to bind erythrocytes in a sialic acid dependent, trypsin resistant, chymotrypsin sensitive manner.
The importance of PfRH4 was realized by its upregulation in experiments that mediated an invasion switch in the Dd2 (W2mef) clone from sialic acid dependent to sialic acid independent pathways [19], [20].
This was clearly demonstrated for PfRH4, whose upregulation was found to mediate a switch from a sialic acid dependent to sialic acid independent invasion phenotype in case of the P. falciparum clone, Dd2 [20], [20].
