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Addlestone, United Kingdom

Knobloch H.,Cranfield University | Schroedl W.,University of Leipzig | Turner C.,Open University Milton Keynes | Chambers M.,TB Research Group | Reinhold P.,Institute of Molecular Pathogenesis at the Friedrich Loeffler Institute FLI
Sensors and Actuators, B: Chemical | Year: 2010

This study aimed (i) to assess the ability of electronic nose (e-nose) technology to differentiate between blood samples of experimentally infected and non-infected subjects and (ii) to evaluate e-nose responses given by volatile organic compounds in relation to the acute phase reaction generated in the host. In an animal model of gram-negative bacterial infection (20 calves; intratracheal inoculation of Mannheimia haemolytica A1), the concentrations of the acute phase proteins (APPs; i.e. lipopolysaccharide binding protein and haptoglobin) were measured in serum samples before and after challenge, and headspaces of pre- and post-inoculation serum samples were analysed using a conducting polymer-based e-nose. Significant changes of certain e-nose sensor responses allowed discrimination between samples before and after challenge. The maximal changes in responses of sensitive e-nose sensors corresponded to the peak of clinical signs. Significant correlations linked decreasing responses of multiple e-nose sensors to increasing concentrations of APPs in the peripheral blood. © 2009.

A number of single-nucleotide polymorphisms (SNPs) have been identified in the genome of Mycobacterium bovis BCG Pasteur compared with the sequenced strain M. bovis 2122/97. The functional consequences of many of these mutations remain to be described; however, mutations in genes encoding regulators may be particularly relevant to global phenotypic changes such as loss of virulence, since alteration of a regulator's function will affect the expression of a wide range of genes. One such SNP falls in bcg3145, encoding a member of the AfsR/DnrI/SARP class of global transcriptional regulators, that replaces a highly conserved glutamic acid residue at position 159 (E159G) with glycine in a tetratricopeptide repeat (TPR) located in the bacterial transcriptional activation (BTA) domain of BCG3145. TPR domains are associated with protein-protein interactions, and a conserved core (helices T1-T7) of the BTA domain seems to be required for proper function of SARP-family proteins. Structural modelling predicted that the E159G mutation perturbs the third a-helix of the BTA domain and could therefore have functional consequences. The E159G SNP was found to be present in all BCG strains, but absent from virulent M. bovis and Mycobacterium tuberculosis strains. By overexpressing BCG3145 and Rv3124 in BCG and H37Rv and monitoring transcriptome changes using microarrays, we determined that BCG3145/Rv3124 acts as a positive transcriptional regulator of the molybdopterin biosynthesis moa1 locus, and we suggest that rv3124 be renamed moaR1. The SNP in bcg3145 was found to have a subtle effect on the activity of MoaR1, suggesting that this mutation is not a key event in the attenuation of BCG. © 2010 Crown copyright.

Dean G.S.,TB Research Group | Clifford D.,TB Research Group | Whelan A.O.,TB Research Group | Whelan A.O.,UK Defence Science and Technology Laboratory | And 9 more authors.
PLoS ONE | Year: 2015

The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission. © 2015 Dean et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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