Browsing by Subject "metabolome"

Now showing 1 - 4 of 4
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    Determination of an Interaction Network between an Extracellular Bacterial Pathogen and the Human Host
    (American Society for Microbiology, 2019-06-18) Griesenauer, Brad; Tran, Tuan M.; Fortney, Kate R.; Janowicz, Diane M.; Johnson, Paula; Gao, Hongyu; Barnes, Stephen; Wilson, Landon S.; Liu, Yunlong; Spinola, Stanley M.; Microbiology and Immunology, School of Medicine
    A major gap in understanding infectious diseases is the lack of information about molecular interaction networks between pathogens and the human host. Haemophilus ducreyi causes the genital ulcer disease chancroid in adults and is a leading cause of cutaneous ulcers in children in the tropics. We developed a model in which human volunteers are infected on the upper arm with H. ducreyi until they develop pustules. To define the H. ducreyi and human interactome, we determined bacterial and host transcriptomic and host metabolomic changes in pustules. We found that in vivo H. ducreyi transcripts were distinct from those in the inocula, as were host transcripts in pustule and wounded control sites. Many of the upregulated H. ducreyi genes were found to be involved in ascorbic acid and anaerobic metabolism and inorganic ion/nutrient transport. The top 20 significantly expressed human pathways showed that all were involved in immune responses. We generated a bipartite network for interactions between host and bacterial gene transcription; multiple positively correlated networks contained H. ducreyi genes involved in anaerobic metabolism and host genes involved with the immune response. Metabolomic studies showed that pustule and wounded samples had different metabolite compositions; the top ion pathway involved ascorbate and aldarate metabolism, which correlated with the H. ducreyi transcriptional response and upregulation of host genes involved in ascorbic acid recycling. These data show that an interactome exists between H. ducreyi and the human host and suggest that H. ducreyi exploits the metabolic niche created by the host immune response.IMPORTANCE Dual RNA sequencing (RNA-seq) offers the promise of determining an interactome at a transcriptional level between a bacterium and the host but has yet to be done on any bacterial infection in human tissue. We performed dual RNA-seq and metabolomics analyses on wounded and infected sites following experimental infection of the arm with H. ducreyi Our results suggest that H. ducreyi survives in an abscess by utilizing l-ascorbate as an alternative carbon source, possibly taking advantage of host ascorbic acid recycling, and that H. ducreyi also adapts by upregulating genes involved in anaerobic metabolism and inorganic ion and nutrient transport. To our knowledge, this is the first description of an interaction network between a bacterium and the human host at a site of infection.
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    Integrative "omic" analysis reveals distinctive cold responses in leaves and roots of strawberry, Fragaria × ananassa 'Korona'
    (Frontiers Media SA, 2015) Koehler, Gage; Rohloff, Jens; Wilson, Robert C.; Kopka, Joachim; Erban, Alexander; Winge, Per; Bones, Atle M.; Davik, Jahn; Alsheikh, Muath K.; Randall, Stephen K.; Department of Biology, School of Science
    To assess underlying metabolic processes and regulatory mechanisms during cold exposure of strawberry, integrative "omic" approaches were applied to Fragaria × ananassa Duch. 'Korona.' Both root and leaf tissues were examined for responses to the cold acclimation processes. Levels of metabolites, proteins, and transcripts in tissues from plants grown at 18°C were compared to those following 1-10 days of cold (2°C) exposure. When leaves and roots were subjected to GC/TOF-MS-based metabolite profiling, about 160 compounds comprising mostly structurally annotated primary and secondary metabolites, were found. Overall, 'Korona' showed a modest increase of protective metabolites such as amino acids (aspartic acid, leucine, isoleucine, and valine), pentoses, phosphorylated and non-phosphorylated hexoses, and distinct compounds of the raffinose pathway (galactinol and raffinose). Distinctive responses were observed in roots and leaves. By 2DE proteomics a total of 845 spots were observed in leaves; 4.6% changed significantly in response to cold. Twenty-one proteins were identified, many of which were associated with general metabolism or photosynthesis. Transcript levels in leaves were determined by microarray, where dozens of cold associated transcripts were quantitatively characterized, and levels of several potential key contributors (e.g., the dehydrin COR47 and GADb) to cold tolerance were confirmed by qRT-PCR. Cold responses are placed within the existing knowledge base of low temperature-induced changes in plants, allowing an evaluation of the uniqueness or generality of Fragaria responses in photosynthetic tissues. Overall, the cold response characteristics of 'Korona' are consistent with a moderately cold tolerant plant.
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    Most Individuals With Advanced Cirrhosis Have Sleep Disturbances, Which Are Associated With Poor Quality of Life
    (Elsevier, 2017) Ghabril, Marwan; Jackson, Mollie; Gotur, Raghavender; Weber, Regina; Orman, Eric; Vuppalanchi, Raj; Chalasani, Naga; Department of Medicine, IU School of Medicine
    Background & Aims Sleep disturbances are common in patients with cirrhosis, but their determinants and effects on health-related quality of life are not well-understood. We investigated the prevalence of disturbed sleep in these patients, factors associated with sleep disruption, and effects on quality of life. Methods We performed a prospective, cross-sectional study of 193 stable ambulatory patients with cirrhosis (154 with decompensated cirrhosis). Participants completed the Pittsburgh Sleep Quality Index (to assess sleep quality), the Chronic Liver Disease Questionnaire (CLDQ), and muscle cramp questionnaires and underwent neurocognitive testing. Actigraphy was performed in a subset of patients with normal and disturbed sleep. We collected serum samples from subjects with normal and disturbed sleep and performed non-targeted metabolomic analyses. Results Of the study subjects, 157 (81%) had disturbed sleep, with Pittsburgh Sleep Quality Index scores >5. Disturbed sleep was associated with muscle cramps, daytime somnolence, and decreased quality of life on the basis of CLDQ scores. Factors independently associated with disturbed sleep in logistic regression analysis included hypoalbuminemia, opiate therapy, and muscle cramps. Disturbed sleep was independently associated with CLDQ score (correlation parameter, –36.6; 95% confidence interval, –24 to –49; P < .001) on linear regression. Disturbed sleep was associated with neurocognitive impairment and with significantly delayed bedtime and decreased total sleep time, measured by actigraphy. Disturbed sleep was associated with metabolome signatures of alterations to the intestinal microbiome and lipid, arginine, and urea cycle metabolism. Conclusions Most patients with advanced cirrhosis (81%) have disturbed sleep. This has negative effects on quality of life and is associated with disruptions of several metabolic pathways, including metabolism by the intestinal microbiota.
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    Serum metabolic signatures of primary biliary cirrhosis and primary sclerosing cholangitis
    (Wiley, 2015-01) Bell, Lauren N.; Wulff, Jacob; Comerford, Megan; Vuppalanchi, Raj; Chalasani, Naga; Department of Medicine, IU School of Medicine
    BACKGROUND & AIMS: A greater understanding of cholestatic disease is necessary to advance diagnostic tools and therapeutic options for conditions such as primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The purpose of this study was to determine and compare the serum metabolomes of patients with PBC (n = 18) or PSC (n = 21) and healthy controls (n = 10) and to identify metabolites that may differentiate these two cholestatic diseases. METHODS AND RESULTS: Using a mass spectrometry-based, non-targeted biochemical profiling approach, we identified 420 serum metabolites, 101 that differed significantly (P ≤ 0.05) between PBC and control groups, 115 that differed significantly between PSC and control groups, and 56 that differed significantly between PSC and PBC groups. Random forest classification analysis was able to distinguish patients with PBC or PSC with 95% accuracy with selected biochemicals reflective of protein and amino acid metabolism identified as the major contributors. Metabolites related to bile acid metabolism, lipid metabolism, inflammation, and oxidative stress/lipid peroxidation were also identified as differing significantly when comparing the disease groups and controls, with some of these pathways differentially affected in the PBC and PSC groups. CONCLUSION: In this study, we identified novel metabolic changes associated with cholestatic disease that were both consistent and different between PBC and PSC. Validation studies in larger patient cohorts are required to determine the utility of these biochemical markers for diagnosis and therapeutic monitoring of patients with PBC and PSC.