Brewer Matthew T, Agbedanu Prince N, Zamanian Mostafa, Day Tim A, Carlson Steve A
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
Eukaryot Cell. 2013 Nov;12(11):1433-8. doi: 10.1128/EC.00150-13. Epub 2013 Aug 23.
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.
溶组织内阿米巴是阿米巴痢疾的病原体,这是一种全球范围内的原生动物疾病,每年导致约10万例死亡。溶组织内阿米巴的毒力可能归因于与宿主细菌菌群的相互作用,即滋养体将结肠细菌作为营养源吞噬。吞噬过程取决于滋养体对激活吞噬途径的细菌表位的识别。溶组织内阿米巴GPCR-1(EhGPCR-1)先前被认为是溶组织内阿米巴在吞噬过程中使用的一种假定的G蛋白偶联受体(GPCR)。在本研究中,我们试图通过在酿酒酵母中进行异源GPCR表达来表征EhGPCR-1。我们发现细菌脂多糖(LPS)是EhGPCR-1的激活剂,并且LPS以浓度依赖的方式刺激EhGPCR-1。此外,我们证明溶组织内阿米巴更喜欢吞噬具有完整LPS的细菌,并且这种吞噬过程对苏拉明敏感,苏拉明可阻止GPCR与G蛋白的相互作用。因此,EhGPCR-1是一种识别LPS的GPCR,是治疗阿米巴病的潜在药物靶点,特别是考虑到针对GPCR的药物已得到充分确立。