title: Adaptive responses to glucose restriction enhance cell survival, antioxidant capability, and autophagy of the protozoan parasite Trichomonas vaginalis.
abstract: BACKGROUND
  To establish an infection in the vagina, Trichomonas vaginalis must adapt to various environmental cues for survival and further replication. Nutrient competition by lactobacilli, the major normal vaginal flora, is one of the mechanisms to limit the growth of other microorganisms. Additionally, lactobacilli produce H2O2 that can reduce the genital infections caused by other pathogens. Thus, the ability to overcome the metabolic stresses, such as glucose restriction (GR), as well as the oxidative stresses, is critical for T. vaginalis to establish an infection.
  
  
  METHODS
  To gain insights into the molecular mechanisms of adaptation to GR, we utilized next-generation RNA sequencing (RNA-seq) to quantify the gene expression changes upon GR. Autophagy, a cytoprotective response to starvation, was monitored by using autophagy-specific staining, autophagy inhibition assay, and co-localization of autophagosomes with lysosomes.
  
  
  RESULTS
  We demonstrated that GR promotes the survival of T. vaginalis. Besides, GR-cultivated cells exhibit higher H2O2 resistance. Our RNA-seq data revealed that genes involved in general energy metabolism were downregulated, whereas genes encoding glutamate metabolism-related aminotransferases were strikingly upregulated under GR. Furthermore, autophagy was first identified and characterized in T. vaginalis under GR.
  
  
  CONCLUSIONS
  These data suggest that GR induces a metabolic reprogramming, enhancing antioxidant ability and autophagy for cellular homeostasis to maintain survival.
  
  
  CONCLUSIONS
  Our work not only led to significant advances in understanding the transcriptional changes in response to GR but also provided possible strategies elicited by GR for T. vaginalis to adapt to the vaginal microenvironment.
authors: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan; Molecular Regulation and Bioinformatics Laboratory, Department of Parasitology, College of Medicine, Chang Gung University, Kwei-Shan, Taoyuan 333, Taiwan.
authors: Kuo-Yang
authors: KY
authors: Huang
authors: Yi-Ywan Margaret
authors: YY
authors: Chen
authors: Yi-Kai
authors: YK
authors: Fang
authors: Wei-Hung
authors: WH
authors: Cheng
authors: Chih-Chieh
authors: CC
authors: Cheng
authors: Yu-Chuen
authors: YC
authors: Chen
authors: Tiffany E
authors: TE
authors: Wu
authors: Fu-Man
authors: FM
authors: Ku
authors: Shih-Chieh
authors: SC
authors: Chen
authors: Rose
authors: R
authors: Lin
authors: Petrus
authors: P
authors: Tang
mesh_terms: D000222:Adaptation, Physiological; D000975:Antioxidants / Q000494:pharmacology*; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival; D004734:Energy Metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D016877:Oxidants / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014246:Trichomonas vaginalis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016877:Oxidants; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D005969:Glutamate Dehydrogenase; D005947:Glucose; D010100:Oxygen
keywords: ADH; ALDO; ALT; Alanine aminotransferase; Alcohol dehydrogenase; Autophagy; CR; ENO; Enolase; Fructose-1,6-bisP aldolase; GAPDH; GDH; GK; GPI; GR; Glucokinase; Glucose phosphate isomerase; Glucose restriction; Glutamate dehydrogenase; Glyceraldehyde 3-P dehydrogenase; LDH; Lactate dehydrogenase; MDH; ME; Malate dehydrogenase; Malic enzyme; NGS; PEPCK; PFK; PGAM; PGK; PK; Phosphoenolpyruvate carboxykinase; Phosphofructokinase; Phosphoglycerate kinase; Pyruvate kinase; RNA sequencing; RNA-seq; ROS; Rbr; SOD; Superoxide dismutase; T. vaginalis; TPI; Thioredoxin peroxidase; Triose-phosphate isomerase; TrxP; caloric restriction; glucose restriction; next generation sequencing; phosphoglycerate mutase; reactive oxygen species; rubrerythrin