Trichomonas vaginalis Metalloproteinase Induces mTOR Cleavage of SiHa Cells

Abstract

Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite.

Cell death offers exceptional cellular and molecular windows for pharmacological interventions in protozoan parasites

“…The bioinformatic evidence disclosed the existence of putative homologs of ATG genes, including TgATG1, TgATG3, TgATG7, TgATG8, TgATG18, TgATG20, and TgVPS34 and the absence of TgATG5 and TgATG12 [87,88], which supports the notion of the evolutionarily conservation of autophagy. It has been demonstrated that L. major and Trichomonas vaginalis employed metalloprotease gp63 to disrupt the Akt/mTOR pathway [89,90], thereby enhancing parasite infectivity and survival. Not surprisingly, hijacking the Tor signaling cascade by certain protozoan parasites has thus far opened modern avenues for the development of new Tor-based therapies to combat protozoan infection.…”

Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with <i>Trichomonas vaginalis</i>

“…In addition, TNF-α levels were almost at basal levels in T. vaginalis MOI 10 after 2 hr incubation. These data meant that a high number of parasites may produce higher levels of proteinases and induce intensive cell death [ 19 , 20 ].…”