Comparative Metabolomics and Proteomics Reveal Vibrio parahaemolyticus Targets Hypoxia-Related Signaling Pathways of Takifugu obscurus

Coronavirus disease 2019 (COVID-19) raises the issue of how hypoxia destroys normal physiological function and host immunity against pathogens. However, there are few or no comprehensive omics studies on this effect. From an evolutionary perspective, animals living in complex and changeable marine environments might develop signaling pathways to address bacterial threats under hypoxia. In this study, the ancient genomic model animal Takifugu obscurus and widespread Vibrio parahaemolyticus were utilized to study the effect. T. obscurus was challenged by V. parahaemolyticus or (and) exposed to hypoxia. The effects of hypoxia and infection were identified, and a theoretical model of the host critical signaling pathway in response to hypoxia and infection was defined by methods of comparative metabolomics and proteomics on the entire liver. The changing trends of some differential metabolites and proteins under hypoxia, infection or double stressors were consistent. The model includes transforming growth factor-β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), and epidermal growth factor (EGF) signaling pathways, and the consistent changing trends indicated that the host liver tended toward cell proliferation. Hypoxia and infection caused tissue damage and fibrosis in the portal area of the liver, which may be related to TGF-β1 signal transduction. We propose that LRG (leucine-rich alpha-2-glycoprotein) is widely involved in the transition of the TGF-β1/Smad signaling pathway in response to hypoxia and pathogenic infection in vertebrates as a conserved molecule.

Integrative Analysis of the Metabolome and Transcriptome of a Cultivated Pepper and Its Wild Progenitor Chiltepin (Capsicum annuum L. var. glabriusculum) Revealed the Loss of Pungency During Capsicum Domestication

Pungency is a unique characteristic of chili peppers (Capsicum spp.) caused by capsaicinoids. The evolutionary emergence of pungency is thought to be a derived trait within the genus Capsicum. However, it is not well-known how pungency has varied during Capsicum domestication and specialization. In this study, we applied a comparative metabolomics along with transcriptomics analysis to assess various changes between two peppers (a mildly pungent cultivated pepper BB3 and its hot progenitor chiltepin) at four stages of fruit development, focusing on pungency variation. A total of 558 metabolites were detected in two peppers. In comparison with chiltepin, capsaicinoid accumulation in BB3 was almost negligible at the early stage. Next, 412 DEGs associated with the capsaicinoid accumulation pathway were identified through coexpression analysis, of which 18 genes (14 TFs, 3 CBGs, and 1 UGT) were deemed key regulators due to their high coefficients. Based on these data, we speculated that downregulation of these hub genes during the early fruit developmental stage leads to a loss in pungency during Capsicum domestication (from chiltepin to BB3). Of note, a putative UDP-glycosyltransferase, GT86A1, is thought to affect the stabilization of capsaicinoids. Our results lay the foundation for further research on the genetic diversity of pungency traits during Capsicum domestication and specialization.

Comparative Metabolomics Analysis of Citrus Varieties

Many citrus varieties are hybridized to improve their quality and to overcome the effects of climate change. However, there is limited information on the effect of the chemical profiles of hybrid varieties on their quality. In this study, we analyzed 10 citrus varieties and evaluated the correlation with their general characteristics and antioxidant activities. Chemical profiles, including the contents of sugars, organic acid compounds, flavonoids, limonoids, and carotenoids, which are related to taste, color, and health benefits, were significantly different depending on the citrus varieties, leading to different antioxidant capacities and general quality parameters. Based on these data, the correlations were investigated, and 10 citrus varieties were clustered into four groups—Changshou kumquat and Jeramon (cluster I); Setoka (cluster II-1); Natsumi, Satsuma mandarin, and Navel orange (cluster Ⅱ-2); Kanpei, Tamnaneunbong, Saybyeolbong, and Shiranui (cluster II-3). Moreover, a metabolomic pathway was proposed. Although citrus peels were not analyzed and the sensory and functional qualities of the citrus varieties were not investigated in this study, our results are useful to better understand the relationship between citrus quality and metabolite profiles, which can provide basic information for the development and improvement of new citrus varieties.

Metabolomic profiling of Burkholderia cenocepacia in synthetic cystic fibrosis sputum medium reveals nutrient environment-specific production of virulence factors

Infections by Burkholderia cenocepacia lead to life-threatening disease in immunocompromised individuals, including those living with cystic fibrosis (CF). While genetic variation in various B. cenocepacia strains has been reported, it remains unclear how the chemical environment of CF lung influences the production of small molecule virulence factors by these strains. Here we compare metabolomes of three clinical B. cenocepacia strains in synthetic CF sputum medium (SCFM2) and in a routine laboratory medium (LB), in the presence and absence of the antibiotic trimethoprim. Using a mass spectrometry-based untargeted metabolomics approach, we identify several compound classes which are differentially produced in SCFM2 compared to LB media, including siderophores, antimicrobials, quorum sensing signals, and various lipids. Furthermore, we describe that specific metabolites are induced in the presence of the antibiotic trimethoprim only in SCFM2 when compared to LB. Herein, C13-acyl-homoserine lactone, a quorum sensing signal previously not known to be produced by B. cenocepacia as well as pyochelin-type siderophores were exclusively detected during growth in SCFM2 in the presence of trimethoprim. The comparative metabolomics approach described in this study provides insight into environment-dependent production of secondary metabolites by B. cenocepacia strains and suggests future work which could identify personalized strain-specific regulatory mechanisms involved in production of secondary metabolites. Investigations into whether antibiotics with different mechanisms of action induce similar metabolic alterations will inform development of combination treatments aimed at effective clearance of Burkholderia spp. pathogens.