DEVELOPMENT AND CHARACTERIZATION OF PAROMOMYCIN-RESISTANT LEISHMANIA-DONOVANI PROMASTIGOTES

Paromomycin is on antileishmanial chemotherapeutic agent. Leishmania d onovani promastigotes resistant to 800 mu M of paromomycin were select ed by increasing drug pressure and cloned. These promastigotes did not acquire multidrug resistance. Paromomycin resistance was stable in th e absence of the drug in the culture. It remained stable also in amast igotes isolated after a passage in mice. Furthermore the resistant par asites were still infective to macrophages in vitro and for mice in vi vo. A sensitive method to detect and to quantify intracellular paromom ycin by HPLC was developed and allowed to show that the main mechanism of resistance seems to be due to decreased drug uptake probably as a consequence of altered membrane composition.