Novel alleles of Plasmodium falciparum dhfr that confer resistance to chlorcycloguanil

None of the alleles generated in this study was as resistant to chlorcycloguanil as the common quadruple mutant, 51I/59R/108N/164L. In addition, selection of high levels of chlorcycloguanil resistance in parasites that carry the 51I/59R/108N allele will require two directed steps, a change from 108N to 108T followed by a mutation from A16 to 16V. The resulting allele, 16V/51I/59R/108T is highly resistant to chlorcycloguanil, but 200-fold more sensitive to pyrimethamine than the 51I/59R/108N allele.