EFFLUX SYSTEMS AND INCREASED TRYPANOTHIONE LEVELS IN ARSENITE-RESISTANT LEISHMANIA

The mechanism of resistance to the metal arsenite has been studied and compared in L. mexicana, L. tropica, and L. tarentolae selected in a step by step manner for arsenite resistance. Amplification of the ABC transporter gene pgpA was found to be a frequent resistance mechanism in all species. Transfection of pgpA genes into different species indi cated that both the origin of the pgpA gene and the recipient strain i nto which the gene is transfected seem important for resistance. An in crease in the levels of trypanothione was also correlated with metal r esistance in different Leishmania species. The mechanism used to incre ase the levels of trypanothione seems to differ, however, between the different species. This study points to a key role of transporters and thiol levels in metal resistance in Leishmania. (C) 1997 Academic Pre ss.