The Faecal Microbiome of the Wild European Badger Meles meles: A Comparison Against Other Wild Omnivorous Mammals from Across the Globe.

Here we investigate the faecal microbiome of wild European badgers Meles meles using samples collected at post-mortem as part of the All Wales Badger Found Dead study. This is the first published characterisation of the badger microbiome. We initially undertook a sex-matched age comparison between the adult and cub microbiomes, based on sequencing the V3-V4 region of the 16S rRNA gene.

High-resolution transcriptomics of bovine purified protein derivative-stimulated peripheral blood from cattle infected with Mycobacterium bovis across an experimental time course.

Objectives: Improved bovine tuberculosis (bTB) diagnostics with higher sensitivity and specificity are urgently required. A better understanding of the peripheral blood transcriptional response of Mycobacterium bovis-infected animals after bovine purified protein derivative (PPD-b) stimulation of whole blood-an important component of current bTB diagnostics-will provide new information for development of better diagnostics.

Methods: RNA sequencing (RNA-seq) was used to study the peripheral blood transcriptome after stimulation with PPD-b across four time points (-1 wk pre-infection, and +1 wk, +2 wk, and +10 wk post-infection) from a 14-week M.

Untargeted metabolomic analysis of thoracic blood from badgers indicate changes linked to infection with bovine tuberculosis (Mycobacterium bovis): a pilot study.

Introduction: Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB) in cattle, represents a major disease burden to UK cattle farming, with considerable costs associated with its control. The European badger (Meles meles) is a known wildlife reservoir for bTB and better knowledge of the epidemiology of bTB through testing wildlife is required for disease control. Current tests available for the diagnosis of bTB in badgers are limited by cost, processing time or sensitivities.

Defining the Genes Required for Survival of Mycobacterium bovis in the Bovine Host Offers Novel Insights into the Genetic Basis of Survival of Pathogenic Mycobacteria.

Tuberculosis has severe impacts on both humans and animals. Understanding the genetic basis of survival of both Mycobacterium tuberculosis, the human-adapted species, and Mycobacterium bovis, the animal-adapted species, is crucial to deciphering the biology of both pathogens. There are several studies that identify the genes required for survival of M.

Metabotyping the Welsh population of badgers based on thoracic fluid.

Introduction: The European badger (Meles meles) is a known wildlife reservoir for bovine tuberculosis (bTB) and a better understanding of the epidemiology of bTB in this wildlife species is required for disease control in both wild and farmed animals. Flow infusion electrospray-high-resolution mass spectrometry (FIE-HRMS) may potentially identify novel metabolite biomarkers based on which new, rapid, and sensitive point of care tests for bTB infection could be developed.

Objectives: In this foundational study, we engaged on assessing the baseline metabolomic variation in the non-bTB infected badger population ("metabotyping") across Wales.

Probing Differences in Gene Essentiality Between the Human and Animal Adapted Lineages of the Complex Using TnSeq.

Members of the complex (MTBC) show distinct host adaptations, preferences and phenotypes despite being >99% identical at the nucleic acid level. Previous studies have explored gene expression changes between the members, however few studies have probed differences in gene essentiality. To better understand the functional impacts of the nucleic acid differences between and , we used the Mycomar T7 phagemid delivery system to generate whole genome transposon libraries in laboratory strains of both species and compared the essentiality status of genes during growth under identical conditions.

Host Serum Proteins as Potential Biomarkers of Bovine Tuberculosis Resistance Phenotype.

Eradication of bovine tuberculosis (bTB) continues to be a worldwide challenge. The lack of reliable vaccines dampens the control and eradication programs of infection and spread. Selection and breeding of cattle resistant to infection would greatly enhance the effectiveness of bTB eradication programs.

Metabolomic Changes in Naturally MAP-Infected Holstein-Friesian Heifers Indicate Immunologically Related Biochemical Reprogramming.

Johne's disease, caused by subsp. (MAP), causes weight loss, diarrhoea, and reduced milk yields in clinically infected cattle. Asymptomatic, subclinically infected cattle shed MAP bacteria but are frequently not detected by diagnostic tests.

Macrophage-specific responses to human- and animal-adapted tubercle bacilli reveal pathogen and host factors driving multinucleated cell formation.

The Mycobacterium tuberculosis complex (MTBC) is a group of related pathogens that cause tuberculosis (TB) in mammals. MTBC species are distinguished by their ability to sustain in distinct host populations. While Mycobacterium bovis (Mbv) sustains transmission cycles in cattle and wild animals and causes zoonotic TB, M.

Immunogenicity and Protection against Challenge in Goats Vaccinated with BCG and Revaccinated after One Year.

Vaccination has been proposed as a supplementary tool for the control of tuberculosis in livestock. The long-term immunogenicity elicited by bacillus Calmette-Guerin (BCG) and the efficacy of revaccination were investigated in thirty goat kids distributed into three groups: unvaccinated controls, BCG (vaccinated at week 0) and BCG-BCG (vaccinated at weeks 0 and 56). Sixty-four weeks after the first vaccination, all animals were challenged with and examined post-mortem (pathology and bacterial load) at week 73.

Association of immune responses of Zebu and Holstein-Friesian cattle and resistance to mycobacteria in a BCG challenge model.

Mycobacterium bovis is the main cause of bovine tuberculosis (BTB) in cattle and can also infect humans. Zebu cattle are considered more resistant to some infectious diseases compared with Holstein-Friesian (HF) cattle, including BTB. However, epidemiological studies may not take into account usage differences of the two types of cattle.

Author Correction: Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic screening for the protective antigenic targets of BCG vaccination.

Bovine tuberculosis is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost of control programmes. Control could be greatly improved by the introduction of an efficacious cattle vaccine but the most likely candidate, BCG, has several limitations including variable efficacy.

Development of a diagnostic compatible BCG vaccine against Bovine tuberculosis.

Bovine tuberculosis (BTB) caused by Mycobacterium bovis remains a major problem in both the developed and developing countries. Control of BTB in the UK is carried out by test and slaughter of infected animals, based primarily on the tuberculin skin test (PPD). Vaccination with the attenuated strain of the M.

Evaluating the sensitivity of the bovine BCG challenge model using a prime boost Ad85A vaccine regimen.

In the absence of biomarkers of protective immunity, newly developed vaccines against bovine tuberculosis need to be evaluated in virulent Mycobacterium bovis challenge experiments, which require the use of expensive and highly in demand Biological Safety Level 3 (BSL3) animal facilities. The recently developed bovine BCG challenge model offers a cheaper and faster way to test new vaccine candidates and additionally reduces the severity of the challenge compared to virulent M. bovis challenge in line with the remits of the NC3Rs.

The Humoral Immune Response to BCG Vaccination.

Bacillus Calmette Guérin (BCG) is the only currently available vaccine against tuberculosis (TB), but it confers incomplete and variable protection against pulmonary TB in humans and bovine TB (bTB) in cattle. Insights into the immune response induced by BCG offer an underexploited opportunity to gain knowledge that may inform the design of a more efficacious vaccine, which is urgently needed to control these major global epidemics. Humoral immunity in TB and bTB has been neglected, but recent studies supporting a role for antibodies in protection against TB has driven a growing interest in determining their relevance to vaccine development.

Transposon libraries identify novel Mycobacterium bovis BCG genes involved in the dynamic interactions required for BCG to persist during in vivo passage in cattle.

Background: BCG is the most widely used vaccine of all time and remains the only licensed vaccine for use against tuberculosis in humans. BCG also protects other species such as cattle against tuberculosis, but due to its incompatibility with current tuberculin testing regimens remains unlicensed. BCG's efficacy relates to its ability to persist in the host for weeks, months or even years after vaccination.

The expression of Indoleamine 2, 3-dioxygenase (IDO) is reduced in granulomas from BCG vaccinated cattle compared to granulomas from unvaccinated controls after experimental challenge with Mycobacterium bovis.

Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis (M. bovis), is a major economic disease of livestock worldwide. Vaccination is considered as a potentially sustainable adjunct to the current control strategy.

Ag85A-specific CD4 T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 T cells post-boosting. Here, the capacity of Ag85A-specific CD4 T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated.

Experimental infection of cattle with Mycobacterium tuberculosis isolates shows the attenuation of the human tubercle bacillus for cattle.

The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis.

A mycobacterial growth inhibition assay (MGIA) for bovine TB vaccine development.

Human tuberculosis remains a significant cause of mortality and morbidity throughout the world. The global economic impact of bovine TB is considerable. An effective vaccine would be the most cost-effective way to control both epidemics, particularly in emerging economies.

Tuberculin Skin Testing Boosts Interferon Gamma Responses to DIVA Reagents in Mycobacterium bovis-Infected Cattle.

BCG vaccination sensitizes cattle to bovine tuberculin, which compromises the use of the current bovine tuberculosis (TB) surveillance tests. Although the performance of a blood test (that utilizes antigens expressed by but not by BCG) capable of discriminating infected from vaccinated animals (DIVA interferon gamma test [DIT]) has been evaluated in naturally infected TB field reactors, there is a need to perform similar analysis in a BCG-vaccinated -infected population. Furthermore, we explored different scenarios under which a DIT may be implemented alongside BCG vaccination: (i) serial testing to resolve potential false-positive skin test results or (ii) a standalone test to replace the single intradermal comparative cervical tuberculin (SICCT) skin test.

Frequency and phenotype of natural killer cells and natural killer cell subsets in bovine lymphoid compartments and blood.

Natural killer (NK) cells are widely distributed in lymphoid and non-lymphoid tissues, but little is known about the recirculation of NK cells between blood and tissues. This is relevant to understanding recirculation in the steady-state and also for determining the roles for NK cells in vaccine-induced immunity and responses to infection. Therefore, the percentage of NK cells and their phenotype across peripheral blood, afferent lymph and lymph nodes in steady-state conditions was investigated in cattle using the pseudo-afferent lymphatic cannulation model.