A novel progesterone receptor membrane component (PGRMC) in the human and swine parasite Taenia solium: implications to the host-parasite relationship

Abstract

BackgroundWe have previously reported that progesterone (P4) has a direct in vitro effect on the scolex evagination and growth of Taenia solium cysticerci. Here, we explored the hypothesis that the P4 direct effect on T. solium might be mediated by a novel steroid-binding parasite protein.MethodsBy way of using immunofluorescent confocal microscopy, flow cytometry analysis, double-dimension electrophoresis analysis, and sequencing the corresponding protein spot, we detected a novel PGRMC in T. solium. Molecular modeling studies accompanied by computer docking using the sequenced protein, together with phylogenetic analysis and sequence alignment clearly demonstrated that T. solium PGRMC is from parasite origin.ResultsOur results show that P4 in vitro increases parasite evagination and scolex size. Using immunofluorescent confocal microscopy, we detected that parasite cells showed expression of a P4-binding like protein exclusively located at the cysticercus subtegumental tissue. Presence of the P4-binding protein in cyst cells was also confirmed by flow cytometry. Double-dimension electrophoresis analysis, followed by sequencing the corresponding protein spot, revealed a protein that was previously reported in the T. solium genome belonging to a membrane-associated progesterone receptor component (PGRMC). Molecular modeling studies accompanied by computer docking using the sequenced protein showed that PGRMC is potentially able to bind steroid hormones such as progesterone, estradiol, testosterone and dihydrodrotestosterone with different affinities. Phylogenetic analysis and sequence alignment clearly demonstrated that T. solium PGRMC is related to a steroid-binding protein of Echinoccocus granulosus, both of them being nested within a cluster including similar proteins present in platyhelminths such as Schistocephalus solidus and Schistosoma haematobium.ConclusionProgesterone may directly act upon T. solium cysticerci probably by binding to PGRMC. This research has implications in the field of host-parasite co-evolution as well as the sex-associated susceptibility to this infection. In a more practical matter, present results may contribute to the molecular design of new drugs with anti-parasite actions.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-2703-1) contains supplementary material, which is available to authorized users.

Proteomic profile associated with cell death induced by androgens in Taenia crassiceps cysticerci: proposed interactome

“…There also appear to be changes in several protein kinases related to the JNK signalling pathway, and to hormone synthesis. The membrane component of the progesterone receptor (PGRMC), a molecule capable of binding steroids to the plasma membranes of cells, has been reported also in other in helminth parasites (Hu et al , 2003; Aguilar-Díaz et al , 2018). One of the bioinformatically identified proteins that seem to show changes in response to androgens in T. crassiceps is precisely this receptor, which could influence the synthesis and degradation mechanisms of T4 and DHT.…”

“…Following this argument, we have recently identified a protein analogue to a progesterone receptor membrane component (PGRMC) in T. solium (Aguilar-Díaz et al , 2018), a phylogenetic relative of T. crassiceps . Furthermore, we found that a spot of the analysed tissues is identical to that protein reported in T. solium .…”

Characterization of Membrane-associated Progesterone Receptor Component-2 (MAPRC2) From Trichinella spiralis and Its Interaction With Progesterone and Mifepristone

“…5). Existing studies also performed the immuno uorescence assay to examine membranebinding progesterone protein in the T. solium cysticerci (23). likewise, many studies reported that progesterone also showed immunomodulatory response during pregnancy diverged towards the Th2 type response to activate the innate immune system (14,58).…”

“…Surprisingly, this receptor membrane(PGRMC-2) was also found in another organism like Caenorhabditis elegans (C. elegans), illustrated to express an analogous protein (vem-1) in mammals (22). In the case of helminths, a few studies present research related to PGRMC receptors (23). Prior studies observed different proteins related to sex hormone receptors comprising PGRMC, progestininduced protein, p48 progesterone-receptor-associated protein, small androgen receptor-interacting proteins that were found in Schistosoma japonicum (24,25).…”

Hormones and Parasites, Their Role in Taenia solium and Taenia crassiceps Physiology and Development

“…In addition, steroids may directly influence the growth and proliferation of parasites. For example, T. crassiceps ORF and WFU cysticerci cell proliferation and metabolism evaluated by 3 H-thymidine and MTT incorporation was increased by the addition of physiological concentrations of testosterone, and 17β-estradiol to the culture media [7] and enhance proliferation of T. crassiceps ORF cysticerci, a progesterone like receptor was found in these parasites [8]. Particularly estrogens are important for T. crassiceps and T. s o l i u m cysticerci development.…”