Combined functional genomic and metabolomic approaches identify new genes required for growth in human urine by multidrug-resistant ST131.

Unlabelled: Urinary tract infections (UTIs) are one of the most common bacterial infections in humans, with ~400 million cases across the globe each year. Uropathogenic (UPEC) is the major cause of UTI and increasingly associated with antibiotic resistance. This scenario has been worsened by the emergence and spread of pandemic UPEC sequence type 131 (ST131), a multidrug-resistant clone associated with extraordinarily high rates of infection.

A Genome-Wide Association Study of Serum Metabolite Profiles in Septic Shock Patients.

Objectives: We sought to assess whether genetic associations with metabolite concentrations in septic shock patients could be used to identify pathways of potential importance for understanding sepsis pathophysiology.

Design: Retrospective multicenter cohort studies of septic shock patients.

Setting: All participants who were admitted to 27 participating hospital sites in three countries (Australia, New Zealand, and the United Kingdom) were eligible for inclusion.

Folate vitamers in the Australian green plum: Through growth and ripening and across locations.

The green plum is a native fruit of Australia that grows on the tree . This study aimed to confirm the high level of folate in green plums by analyzing a large number of ripe samples from multiple locations and to understand how folate vitamers change as the fruit grows through maturity stages. This study analyzed green plums for five vitamers of folate, Hfolate, 5-CH-Hfolate, 5-CHO-Hfolate, 10-CHO-PteGlu, and PteGlu (folic acid) using a stable isotope dilution assay on a liquid chromatograph mass spectrometer (LC-MS).

The Framework for Responsible Research With Australian Native Plant Foods: A Food Chemist's Perspective.

Australia is a rich source of biodiverse native plants that are mostly unstudied by western food science despite many of them being ethnofoods of Australian Indigenous people. Finding and understanding the relevant policy and legal requirements to scientifically assess these plants in a responsible way is a major challenge for food scientists. This work aims to give an overview of what the legal and policy framework is in relation to food chemistry on Australian native plant foods, to clarify the relationships between the guidelines, laws, policies and ethics and to discuss some of the challenges they present in food chemistry.

Access to highly specialized growth substrates and production of epithelial immunomodulatory metabolites determine survival of Haemophilus influenzae in human airway epithelial cells.

Haemophilus influenzae (Hi) infections are associated with recurring acute exacerbations of chronic respiratory diseases in children and adults including otitis media, pneumonia, chronic obstructive pulmonary disease and asthma. Here, we show that persistence and recurrence of Hi infections are closely linked to Hi metabolic properties, where preferred growth substrates are aligned to the metabolome of human airway epithelial surfaces and include lactate, pentoses, and nucleosides, but not glucose that is typically used for studies of Hi growth in vitro. Enzymatic and physiological investigations revealed that utilization of lactate, the preferred Hi carbon source, required the LldD L-lactate dehydrogenase (conservation: 98.

Cyanine-5-Driven Behaviours of Hyperbranched Polymers Designed for Therapeutic Delivery Are Cell-Type Specific and Correlated with Polar Lipid Distribution in Membranes.

The ability to predict the behaviour of polymeric nanomedicines can often be obfuscated by subtle modifications to the corona structure, such as incorporation of fluorophores or other entities. However, these interactions provide an intriguing insight into how selection of molecular components in multifunctional nanomedicines contributes to the overall biological fate of such materials. Here, we detail the internalisation behaviours of polymeric nanomedicines across a suite of cell types and extrapolate data for distinguishing the underlying mechanics of cyanine-5-driven interactions as they pertain to uptake and endosomal escape.

The Nutritional Potential of the Native Australian Green Plum () Compared to Other Anacardiaceae Fruit and Nuts.

The native Australian green plum () is a small fruit that grows in the northern parts of the Northern Territory and Western Australia. The fruit belongs to the family Anacardiaceae, which includes the other agriculturally important fruit mangoes, pistachios and cashew nuts. The green plum is a favored species of fruit for the Aboriginal communities and an important bush food in the Northern Territory.

Using Genome-Scale Metabolic Networks for Analysis, Visualization, and Integration of Targeted Metabolomics Data.

Interpretation of metabolomics data in the context of biological pathways is important to gain knowledge about underlying metabolic processes. In this chapter we present methods to analyze genome-scale models (GSMs) and metabolomics data together. This includes reading and mining of GSMs using the SBTab format to retrieve information on genes, reactions, and metabolites.

Glucose Catabolism Leading to Production of the Immunometabolite Acetate Has a Key Contribution to the Host Airway-Pathogen Interplay.

Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and impaired airway immunity, which provides an opportunistic platform for nontypeable (NTHi) infection. Clinical evidence supports that the COPD airways present increased concentrations of glucose, which may facilitate proliferation of pathogenic bacteria able to use glucose as a carbon source. NTHi metabolizes glucose through respiration-assisted fermentation, leading to the excretion of acetate, formate, and succinate.

Metabolic analyses reveal common adaptations in two invasive Haemophilus influenzae strains.

Non-typeable Haemophilus influenzae (NTHi) is a major pathogen in upper and lower respiratory tract infections in humans, and is increasingly also associated with invasive disease. We have examined two unrelated NTHi invasive disease isolates, R2866 and C188, in order to identify metabolic and physiological properties that distinguish them from respiratory tract disease isolates such as Hi2019. While the general use of the Hi metabolic network was similar across all three strains, the two invasive isolates secreted increased amounts of succinate, which can have anti-inflammatory properties.

Modeling Meets Metabolomics-The WormJam Consensus Model as Basis for Metabolic Studies in the Model Organism .

Metabolism is one of the attributes of life and supplies energy and building blocks to organisms. Therefore, understanding metabolism is crucial for the understanding of complex biological phenomena. Despite having been in the focus of research for centuries, our picture of metabolism is still incomplete.

Seminal plasma enables selection and monitoring of active surveillance candidates using nuclear magnetic resonance-based metabolomics: A preliminary investigation.

Background: Diagnosis and monitoring of localized prostate cancer requires discovery and validation of noninvasive biomarkers. Nuclear magnetic resonance (NMR)-based metabolomics of seminal plasma reportedly improves diagnostic accuracy, but requires validation in a high-risk clinical cohort.

Materials And Methods: Seminal plasma samples of 151 men being investigated for prostate cancer were analyzed with H-NMR spectroscopy.

NMR-Based Metabolomics of Oral Biofluids.

NMR-based metabolomics is an established technique for characterizing the metabolite profile of biological fluids and investigating how metabolite profiles change in response to biological and/or clinical stimuli. Thus, NMR-based metabolomics has the potential to discover biomarkers for diagnosis, prognosis, and/or therapy of clinical conditions, as well as to unravel the physiology underlying clinical conditions. Here, we describe a detailed protocol for NMR-based metabolomics of oral biofluids, including sample collection, sample handling, NMR data acquisition, and processing.

Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers.

Background: Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers.

Can atorvastatin with metformin change the natural history of prostate cancer as characterized by molecular, metabolomic, imaging and pathological variables? A randomized controlled trial protocol.

Background: Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa.

Methods/design: This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy.

Diagnostic performance of expression of PCA3, Hepsin and miR biomarkers inejaculate in combination with serum PSA for the detection of prostate cancer.

Background And Methods: Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens.

Impacts of the Callipyge mutation on ovine plasma metabolites and muscle fibre type.

The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the pelvic limbs and torso, as well as body leanness. The mechanism underpinning enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres.

Comparative Genomics of Serial Isolates of Cryptococcus neoformans Reveals Gene Associated With Carbon Utilization and Virulence.

The opportunistic fungal pathogen Cryptococcus neoformans is a leading cause of mortality among the human immunodeficiency virus/acquired immunodeficiency syndrome population and is known for frequently causing life-threatening relapses. To investigate the potential contribution of in-host microevolution to persistence and relapse, we have analyzed two serial isolates obtained from a patient with acquired immunodeficiency syndrome who suffered an initial and relapse episode of cryptococcal meningoencephalitis. Despite being identical by multilocus sequence typing, the isolates differ phenotypically, exhibiting changes in key virulence factors, nutrient acquisition, metabolic profiles, and the ability to disseminate in an animal model.

Urine metabonomic profiling of a female adolescent with PIT-1 mutation before and during growth hormone therapy: insights into the metabolic effects of growth hormone.

Objective: Growth hormone (GH) is a protein hormone with important roles in growth and metabolism. The objective of this study was to investigate the metabolism of a human subject with severe GH deficiency (GHD) due to a PIT-1 gene mutation and the metabolic effects of GH therapy using Nuclear Magnetic Resonance (NMR)-based metabonomics. NMR-based metabonomics is a platform that allows the metabolic profile of biological fluids such as urine to be recorded, and any alterations in the profile modulated by GH can potentially be detected.

A core metabolic enzyme mediates resistance to phosphine gas.

Phosphine is a small redox-active gas that is used to protect global grain reserves, which are threatened by the emergence of phosphine resistance in pest insects. We find that polymorphisms responsible for genetic resistance cluster around the redox-active catalytic disulfide or the dimerization interface of dihydrolipoamide dehydrogenase (DLD) in insects (Rhyzopertha dominica and Tribolium castaneum) and nematodes (Caenorhabditis elegans). DLD is a core metabolic enzyme representing a new class of resistance factor for a redox-active metabolic toxin.

Performance evaluation of algorithms for the classification of metabolic 1H NMR fingerprints.

Nontargeted metabolite fingerprinting is increasingly applied to biomedical classification. The choice of classification algorithm may have a considerable impact on outcome. In this study, employing nested cross-validation for assessing predictive performance, six binary classification algorithms in combination with different strategies for data-driven feature selection were systematically compared on five data sets of urine, serum, plasma, and milk one-dimensional fingerprints obtained by proton nuclear magnetic resonance (NMR) spectroscopy.

Investigating potential mechanisms of obesity by metabolomics.

Obesity is a serious health problem with an increased risk of several common diseases including diabetes, cardiovascular disease, and cancer. Metabolomics is an emerging analytical technique for systemic determination of metabolite profiles, which is useful for understanding the biochemical changes in obesity or related diseases both in individual organs and at the organism level. Increasingly, this technology has been applied to the study of obesity, complementing transcriptomics and/or proteomics analyses.

Identification of crotonyl glycine in urine of sheep after 48 h road transport.

Thousands of metabolites are excreted in urine, and potentially can be detected in NMR spectra. Currently, NMR spectral information for about one thousand metabolites has been deposited in publicly available sources, limiting the identification of chemical compounds that are potential biomarkers for clinical and subclinical applications. This study reports the identification of crotonyl glycine, one of the key metabolites detected by ¹H NMR as excreted in the urine of sheep after 48 h road transport and during the subsequent 72 h recovery period.

A unique chromosomal rearrangement in the Cryptococcus neoformans var. grubii type strain enhances key phenotypes associated with virulence.

Unlabelled: The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently diversified, forming a species complex containing members with distinct morphologies, distributions, and pathologies of infection. We have investigated structural changes in genomic architecture such as inversions and translocations that distinguish the most pathogenic variety, Cryptococcus neoformans var.

Altered fatty acid metabolism in long duration road transport: An NMR-based metabonomics study in sheep.

The physical, endocrine, and metabolic responses of livestock to road transport have been evaluated by conventional hematological and biochemistry parameters for more than 20 years. However, these measures are relatively insensitive to subtle metabolic adaptations. We applied NMR-based metabonomics to assess system-wide metabolic responses as expressed in urine and serum of a large cohort of animals (n = 80) subjected to 12 and 48 h road transport.