Glucose-restriction increases Trichomonas vaginalis cellular damage towards HeLa cells and proteolytic activity of cysteine proteinases (CPs), such as TvCP2

• Published in: Parasitology Vol. 146; no. 9; pp. 1156 - 1166
• Main Authors: Miranda-Ozuna, Jesús F. T., Rivera-Rivas, Luis Alberto, Cárdenas-Guerra, Rosa Elena, Hernández-García, Mar Sarai, Rodríguez-Cruz, Sarahí, González-Robles, Arturo, Chavez-Munguía, Bibiana, Arroyo, Rossana
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.08.2019
• Subjects: Antibodies; Apoptosis; Cell Membrane - drug effects; Cell Membrane - metabolism; Cysteine; Cysteine Endopeptidases - metabolism; Cytotoxicity; Damage; Environmental factors; Gene expression; Glucose; Glucose - metabolism; Glucose - pharmacology; HeLa Cells; Host-Parasite Interactions; Humans; Infections; Laboratories; Menstruation; Microscopy; Nutrient deficiency; Nutritional Physiological Phenomena; Parasites; Parasitic diseases; Pathogenesis; Polyamines; Polyclonal antibodies; Proteins; Proteolysis; Protozoan Proteins - metabolism; Secretion; Sexually transmitted diseases; STD; Toxicity; Trichomonas vaginalis; Trichomonas vaginalis - enzymology; Trichomonas vaginalis - pathogenicity; United States > US; Mexico; Trichomonas vaginalis; Apoptosis induction; cellular damage; glucose regulation; cytotoxicity; cysteine proteinases
• ISSN: 0031-1820; 1469-8161
• DOI: 10.1017/S0031182019000209

Trichomonas vaginalis induces cellular damage to the host cells (cytotoxicity) through the proteolytic activity of multiple proteinases of the cysteine type (CPs). Some CPs are modulated by environmental factors such as iron, zinc, polyamines, etc. Thus, the goal of this study was to assess the effect of glucose on T. vaginalis cytotoxicity, proteolytic activity and the particular role of TvCP2 (TVAG_057000) during cellular damage. Cytotoxicity assays showed that glucose-restriction (GR) promotes the highest HeLa cell monolayers destruction (~95%) by trichomonads compared to those grown under high glucose (~44%) condition. Zymography and Western blot using different primary antibodies showed that GR increased the proteolytic activity, amount and secretion of certain CPs, including TvCP2. We further characterized the effect of glucose on TvCP2. TvCP2 increases in GR, localized in vesicles close to the plasma membrane and on the surface of T. vaginalis. Furthermore, pretreatment of GR-trichomonads with an anti-TvCP2r polyclonal antibody specifically reduced the levels of cytotoxicity and apoptosis induction to HeLa cells in a concentration-dependent manner. In conclusion, our data show that GR, as a nutritional stress condition, promotes trichomonal cytotoxicity to the host cells, increases trichomonad proteolytic activity and amount of CPs, such as TvCP2 involved in cellular damage.