Anti-Trypanosoma activity of bioactive metabolites from Photorhabdus luminescens and Xenorhabdus nematophila

Exp Parasitol. 2019 Sep:204:107724. doi: 10.1016/j.exppara.2019.107724. Epub 2019 Jul 4.

Abstract

Only two drugs are currently available for the treatment of Chagas disease and their effectiveness are unsatisfactory. Photorhabdus luminescens and Xenorhabdus nematophila, two enteric bacteria highly pathogenic to a broad range of insects, have been studied as potential source for bioactive metabolites against protozoa causing neglected tropical diseases. Therefore, we tested the in vitro anti-Trypanosoma cruzi activity of secreted metabolites from these bacteria. The conditioned medium of X. nematophila and P. luminescens showed significant parasiticidal activity in a concentration-dependent manner (IC50XN = 0.34 mg/mL, IC50PL = 1.0 mg/mL). The parasiticidal compound was identified as a small molecule stable to heating and pH changes ranging from 2 to 12. Moreover, anti-Trypanosoma molecules secreted by both bacteria stimulate the trypanocidal activity of macrophages by a mechanism independent of nitric oxide. Summarizing, our studies reveal that P. luminescens and X. nematophila are potential sources of putative novel drugs against Chagas disease.

Keywords: Chagas disease; Entomopathogenic bacteria; Macrophages; Secondary metabolites; Trypanocidal activity.

MeSH terms

  • Analysis of Variance
  • Animals
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / pharmacology*
  • Bacterial Proteins / therapeutic use
  • Biological Assay
  • Chagas Disease / drug therapy
  • Culture Media, Conditioned
  • Endopeptidase K / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Photorhabdus / chemistry*
  • Temperature
  • Trypanocidal Agents / adverse effects
  • Trypanocidal Agents / pharmacology*
  • Trypanocidal Agents / therapeutic use
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / growth & development
  • Xenorhabdus / chemistry*

Substances

  • Bacterial Proteins
  • Culture Media, Conditioned
  • Trypanocidal Agents
  • Endopeptidase K