First Insights into the Fecal Metabolome of Healthy, Free-Roaming Giraffes (): An Untargeted GCxGC/TOF-MS Metabolomics Study.

Background/objectives: This study provides the first insights to the fecal metabolome of the giraffe (). By using untargeted metabolomics via gas chromatography time-of-flight mass spectrometry (GCxGC/TOF-MS), this study primarily aims to provide results of the impact that external stimuli, such as supplemental feeding (SF) practices, seasonal variation and sex, might have on the fecal metabolome composition of healthy, free-roaming giraffes.

Methods: Untargeted GCxGC/TOF-MS analysis was applied to the feces collected from thirteen giraffes (six males and seven females) from six different locations within the central Free State Province of South Africa over a period of two years.

The effect of Tyloxapol on the metabolome of Mycobacterium tuberculosis.

The use of detergents when culturing Mycobacterium tuberculosis (M. tuberculosis) are essential to prevent clumping. However, these detergents may influence research outcomes by impacting bacterial morphology and metabolism.

Protective efficacy of a plant-produced beta variant rSARS-CoV-2 VLP vaccine in golden Syrian hamsters.

In the quest for heightened protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, we engineered a prototype vaccine utilizing the plant expression system of Nicotiana benthamiana, to produce a recombinant SARS-CoV-2 virus-like particle (VLP) vaccine presenting the S-protein from the Beta (B.1.351) variant of concern (VOC).

Safety Properties of O157:H7 Specific Bacteriophages: Recent Advances for Food Safety.

Shiga-toxin-producing (STEC) is typically detected on food products mainly due to cross-contamination with faecal matter. The serotype O157:H7 has been of major public health concern due to the severity of illness caused, prevalence, and management. In the food chain, the main methods of controlling contamination by foodborne pathogens often involve the application of antimicrobial agents, which are now becoming less efficient.

Metabolomic Profiling of Hormonal Contraceptive Use in Young Females Using a Commercially Available LC-MS/MS Kit.

Oral hormonal contraceptive users carry the risk of venous thrombosis and increased mortality. This study aimed to comprehensively profile the serum metabolome of participants using a combination of drospirenone (DRSP) and ethinyl estradiol (EE) containing oral contraceptives (COCs). The MxP Quant 500 kit for liquid chromatography mass tandem spectrometry (LC-MS/MS) was used to analyse the 22 controls and 44 COC users (22 on a low EE dose (DRSP/20EE) and 22 on a higher EE dose (DRSP/30EE)).

Tuberculosis is associated with sputum metabolome variations, irrespective of patient sex or HIV status: an untargeted GCxGC-TOFMS study.

Introduction: Various studies have identified TB-induced metabolome variations. However, in most of these studies, a large degree of variation exists between individual patients.

Objectives: To identify differential metabolites for TB, independent of patients' sex or HIV status.

Evaluation of BAYESIL for automated annotation of H NMR data using limited sample volumes: application to African elephant serum.

Introduction: Technological advancements enabled the analyses of limited sample volumes on H NMR. Manual spectral profiling of the data is, however, complex, and timely.

Objective: To evaluate the performance of BAYESIL for automated identification and quantification of H NMR spectra of limited volume samples.

Immunogenicity of adjuvanted plant-produced SARS-CoV-2 Beta spike VLP vaccine in New Zealand white rabbits.

The outbreak of the SARS-CoV-2 global pandemic heightened the pace of vaccine development with various vaccines being approved for human use in a span of 24 months. The SARS-CoV-2 trimeric spike (S) surface glycoprotein, which mediates viral entry by binding to ACE2, is a key target for vaccines and therapeutic antibodies. Plant biopharming is recognized for its scalability, speed, versatility, and low production costs and is an increasingly promising molecular pharming vaccine platform for human health.

FACTORS CONTRIBUTING TO PULMONARY TB TREATMENT LOST TO FOLLOW-UP IN DEVELOPING COUNTRIES: AN OVERVIEW.

Background: Despite the available treatment options, pulmonary tuberculosis (TB) remains a leading cause of disease-related deaths worldwide. Treatment non-adherence/lost to follow-up (LTFU), particularly in developing countries, is a continuous concern. LTFU prolongs TB infectiousness and contributes to TB treatment failure, relapse, and death.

Protective immunity of plant-produced African horse sickness virus serotype 5 chimaeric virus-like particles (VLPs) and viral protein 2 (VP2) vaccines in IFNAR mice.

Next generation vaccines have the capability to contribute to and revolutionise the veterinary vaccine industry. African horse sickness (AHS) is caused by an arbovirus infection and is characterised by respiratory distress and/or cardiovascular failure and is lethal to horses. Mandatory annual vaccination in endemic areas curtails disease occurrence and severity.

The effect of combined oral contraceptives containing drospirenone and ethinylestradiol on serum levels of amino acids and acylcarnitines.

Introduction: Metabolome variations have long been associated with normal hormonal fluctuations, and similar effects, related to the use of early generation synthetic hormones as a means of contraception, have also been identified.

Objective: We investigated the serum amino acid and acylcarnitine profiles induced by the use of combined oral contraceptives (COCs) consisting of Ethinylestradiol (EE) and a 4th generation progestin, Drospirenone (DRSP).

Method: Gas chromatography mass spectrometry and liquid chromatography with tandem mass spectrometry was used to identify and quantify the serum amino acids and acyl carnitine levels in 24 controls, 25 DRSP/20EE users and 26 DRSP/30EE users.

Chronological Metabolic Response to Intensive Phase TB Therapy in Patients with Cured and Failed Treatment Outcomes.

Despite the arguable success of the standardized tuberculosis (TB) treatment regime, a significant number of patients still present with treatment failure. To improve on current TB treatment strategies, we sought to gain a better understanding of the hosts' response to TB therapy. A targeted metabolomics approach was used to compare the urinary acylcarnitine and amino acid profiles of eventually cured TB patients with those of patients presenting with a failed treatment outcome, comparing these patient groups at the time of diagnosis and at weeks 1, 2, and 4 of treatment.

The Echo of Pulmonary Tuberculosis: Mechanisms of Clinical Symptoms and Other Disease-Induced Systemic Complications.

Clinical symptoms of active tuberculosis (TB) can range from a simple cough to more severe reactions, such as irreversible lung damage and, eventually, death, depending on disease progression. In addition to its clinical presentation, TB has been associated with several other disease-induced systemic complications, such as hyponatremia and glucose intolerance. Here, we provide an overview of the known, although ill-described, underlying biochemical mechanisms responsible for the clinical and systemic presentations associated with this disease and discuss novel hypotheses recently generated by various omics technologies.

Serum Metabolome Changes in Relation to Prothrombotic State Induced by Combined Oral Contraceptives with Drospirenone and Ethinylestradiol.

The association between hypercoagulability and use of drospirenone (DRSP) and ethinylestradiol (EE) containing combined oral contraceptives (COCs) is an important clinical concern. We have previously reported that the two formulations of DRSP combined with EE (namely, DRSP/20EE and DRSP/30EE) bring about a prothrombotic state in hemostatic traits of female users. We report here the serum metabolomic changes in the same study cohort in relation to the attendant prothrombotic state induced by COC use, thus offering new insights on the underlying biochemical mechanisms contributing to the altered coagulatory profile with COC use.

Metabolomics describes previously unknown toxicity mechanisms of isoniazid and rifampicin.

Isoniazid and rifampicin are well-known anti-mycobacterial agents and are widely used to treat pulmonary tuberculosis (TB) as part of the combined therapy approach, recommended by the World Health Organization. The ingestion of these first-line TB drugs are, however, not free of side effects, and are toxic to the liver, kidney, and central nervous system. These side effects are associated with poor treatment compliance, resulting in TB treatment failure, relapse and drug resistant TB.

Tween 80 induces a carbon flux rerouting in Mycobacterium tuberculosis.

As a means to increase the growth rate and reduce aggregation, Tween 80 is routinely added to growth media during mycobacterial culturing. This detergent has, however, been associated with causing alterations to the morphology, pathogenicity and virulence of these bacteria. In an attempt to better understand the underlying mechanism of these alterations, we investigated the effect of Tween 80 on the metabolomes of a M.

Time-Dependent Changes in Urinary Metabolome Before and After Intensive Phase Tuberculosis Therapy: A Pharmacometabolomics Study.

Pharmacometabolomics is a rapidly emerging omics science signaling the convergence of clinical pharmacology, metabolomics, precision medicine, and biomarker research. Tuberculosis (TB) treatment outcomes have complex biological, environmental, and social determinants and thus, represent a promising application of pharmacometabolomics. In samples of 23 patients undergoing intensive phase TB therapy for 4 weeks, we identified drug-induced host-metabolome variations before and at repeated time intervals post-treatment: (1) an overall reduction in the oxidative stress levels over the course of TB treatment; (2) a time-dependent induction and inhibition of several enzymes in response to the drugs (CYP2E1, CYP3A4, alcohol dehydrogenase, and aminocarboxymuconate-semialdehyde decarboxylase), and altered oxidative stress levels (aconitase, formylglycine-generating enzyme, α-ketoglutarate dehydrogenase, and succinate-semialdehyde dehydrogenase); (3) an upregulated urea cycle; and (4) altered insulin production.

The application of metabolomics toward pulmonary tuberculosis research.

In the quest to identify novel biomarkers for pulmonary tuberculosis (TB), high-throughput systems biology approaches such as metabolomics has become increasingly widespread. Such biomarkers have not only successfully been used for better disease characterization, but have also provided new insights toward the future development of improved diagnostic and therapeutic approaches. In this review, we give a summary of the metabolomics studies done to date, with a specific focus on those investigating various aspects of pulmonary TB, and the infectious agent responsible, Mycobacterium tuberculosis.

Novel insights into the pharmacometabonomics of first-line tuberculosis drugs relating to metabolism, mechanism of action and drug-resistance.

The World Health Organization recommends the directly observed therapy short-course (DOTS) regimen, a combination of four first-line antibiotics (isoniazid, rifampicin, pyrazinamide and ethambutol), for the treatment of active pulmonary tuberculosis (TB). However, despite the fact that this treatment regimen is commonly used worldwide, the metabolism and anti-bacterial mechanisms of these drugs are not yet fully understood. This lack of information ultimately contributes to the poor patient compliance and the subsequent treatment failure and post treatment relapse seen in some TB patients.

Total Metabolome Extraction from Mycobacterial Cells for GC-MS Metabolomics Analysis.

Over the past 10 years, the number of metabolomics based publications in the available scientific literature has exponentially grown, a large portion of which describing new biomarkers better elucidating microbial disease mechanisms and improved diagnostics and treatment thereof. Here, we describe a metabolomics method for extracting the total metabolome (all compounds present in the microbial cell irrespective of the compound class), for analysis in a single analytical run using only one analytical instrument. This method includes disruption of robust microbial cell walls, and the precipitation of proteins and cell debris using a combination of mechanical methods and solvents.

Fatty Acid Metabolome Extraction from Mycobacterial Cells for GC-MS Metabolomics Analysis.

Metabolomics is becoming an increasingly popular research tool for identifying new biomarkers, which can, among other applications, be applied to elucidate various microbial growth and virulence mechanisms. Since the lipid composition of numerous microorganisms are unique and characteristic of the particular species, and in many instances also associated with several of their growth and virulence features, we developed a method for extracting the total free fatty acid metabolome from mycobacterial cells, in order to better characterize these using a gas chromatography-mass spectrometry (GC-MS) metabolomics approach. The described method can be considered an optimized Bligh-Dyer approach, since it uses the traditional solvents; chloroform, methanol and water, in a ratio of 1:2:1.