LEISHMANIA-INFANTUM PROMASTIGOTES HAVE A POOR CAPACITY FOR ANAEROBIC FUNCTIONING AND DEPEND MAINLY ON RESPIRATION FOR THEIR ENERGY GENERATION

In earlier studies on the supposedly anaerobic metabolism of Leishmani a promastigotes it was suggested that the reduction of fumarate to suc cinate functions as the main electron sink during anoxia. Interestingl y, however, our preliminary results demonstrated that rhodoquinone, an essential component for efficient fumarate reduction in eukaryotes, w as absent in L. infantum promastigotes. Therefore, we re-investigated the energy metabolism and succinate production of these promastigotes. Our studies demonstrated that L. infantum promastigotes could, to a c ertain extent, survive periods without respiration but had a low capac ity for anaerobic metabolism. When oxygen could not be used as termina l electron acceptor, the degradation of glucose was severely inhibited , forcing the parasite to reduce its energy expenditure, which resulte d in inhibited motility and proliferation. In addition, we studied the mechanism of succinate production under aerobic conditions and showed that in L. infantum promastigotes this succinate was mainly produced via an oxidative pathway, the Krebs cycle, and not significantly via f umarate reduction, which correlated with the absence of rhodoquinone. Taken collectively our studies show that L. infantum promastigotes dep end mainly on respiratory chain activity for energy generation, have a poor capacity for anaerobic functioning, and go into metabolic arrest during anoxic conditions.