Evidence for a Bacterial Lipopolysaccharide-Recognizing G-protein-coupled Receptor in the Bacterial Engulfment by Entamoeba Histolytica

Eukaryot Cell. 2013 Nov;12(11):1433-8. doi: 10.1128/EC.00150-13. Epub 2013 Aug 23.

Abstract

Entamoeba histolytica is the causative agent of amoebic dysentery, a worldwide protozoal disease that results in approximately 100,000 deaths annually. The virulence of E. histolytica may be due to interactions with the host bacterial flora, whereby trophozoites engulf colonic bacteria as a nutrient source. The engulfment process depends on trophozoite recognition of bacterial epitopes that activate phagocytosis pathways. E. histolytica GPCR-1 (EhGPCR-1) was previously recognized as a putative G-protein-coupled receptor (GPCR) used by Entamoeba histolytica during phagocytosis. In the present study, we attempted to characterize EhGPCR-1 by using heterologous GPCR expression in Saccharomyces cerevisiae. We discovered that bacterial lipopolysaccharide (LPS) is an activator of EhGPCR-1 and that LPS stimulates EhGPCR-1 in a concentration-dependent manner. Additionally, we demonstrated that Entamoeba histolytica prefers to engulf bacteria with intact LPS and that this engulfment process is sensitive to suramin, which prevents the interactions of GPCRs and G-proteins. Thus, EhGPCR-1 is an LPS-recognizing GPCR that is a potential drug target for treatment of amoebiasis, especially considering the well-established drug targeting to GPCRs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Entamoeba histolytica / drug effects
  • Entamoeba histolytica / metabolism*
  • Entamoeba histolytica / microbiology
  • Escherichia coli / pathogenicity
  • Lipopolysaccharides / pharmacology*
  • Molecular Sequence Data
  • Phagocytosis*
  • Protein Binding
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / metabolism*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Suramin / pharmacology

Substances

  • Lipopolysaccharides
  • Protozoan Proteins
  • Receptors, G-Protein-Coupled
  • Suramin