| The development and spread of multiple drug resistant Plasmodium falciparum has compromised the effectiveness of traditional antimalarials. With considerable effort, the mechanisms responsible for drug resistance in P. falciparum to some of the current chemotherapeutics have been determined.; Currently, our understanding of the mechanisms responsible for the initiation of drug resistance is very limited. Rathod et al. (1997) demonstrated that parasite clones that have previously acquired drug resistance to a variety of antimalarial agents acquire drug resistance to two new antimalarials, 5-fluoroorotate and atovaquone, at a greater frequency than parasites susceptible to traditional antimalarials. Their work suggests that multiple drug resistant parasites have some genetic predisposition that underlies their ability to develop resistance to novel antimalarials.; Current acquired drug resistance research focuses on the parasites' ability to modify an essential protein, which protects function but renders the inhibitor ineffective. It would seem that the process for a parasite to become drug-resistant to a nonessential protein would be less complicated. Our work focused on developing cytosine deaminase as a negative selection marker for P. falciparum for the purpose of determining whether a highly drug susceptible parasite (D6) can develop resistance to 5-fluorocytosine. |
