Entomopathogenic bacteriaPhotorhabdus luminescensas drug source againstLeishmania amazonensis

Abstract

AbstractLeishmaniasis is a widely spread and zoonotic disease with serious problems as low effectiveness of drugs, emergence of parasite resistance and severe adverse reactions. In recent years, considerable attention has been given to secondary metabolites produced byPhotorhabdus luminescens, an entomopathogenic bacterium. Here, we assessed the leishmanicidal activity ofP. luminescensculture fluids. Initially, promastigotes ofLeishmania amazonensiswere incubated with cell free conditioned medium ofP. luminescensand parasite survival was monitored. Different pre-treatments of the conditioned medium revealed that the leishmanicidal activity is due to a secreted peptide smaller than 3 kDa. ThePhotorhabdus-derived leishmanicidal toxin (PLT) was enriched from conditioned medium and its effect on mitochondrial membrane potential of promastigotes, was determined. Moreover, the biological activity of PLT against amastigotes was evaluated. PLT inhibited the parasite growth and showed significant leishmanicidal activity against promastigote and amastigotes ofL. amazonensis. PLT also caused mitochondrial dysfunction in parasites, but low toxicity to mammalian cell and human erythrocytes. Moreover, the anti-amastigote activity was independent of nitric oxide production. In summary, our results highlight thatP. luminescenssecretesLeishmania-toxic peptide(s) that are promising novel drugs for therapy against leishmaniasis.