Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives

Stadthagen, Gustavo and Jackson, Mary and Charles, Patricia and Boudoua, Frédéric and Barilonea, Nathalie and Huerree, Michel and Constant, Patricia and Liav, Avraham and Bottova, Iveta and Nigou, Jérome and Brandod, Thérèse and Puzo, Germain and Daffé, Mamadou and Benjamin, Pearline and Coade, Stephen and Buxton, Roger S. and Tascon, Ricardo E. and Rae, Aaron and Robertson, Brian D. and Lowrie, Douglas B. and Young, Douglas B. and Gicquel, Brigitte and Griffin, R. (2006) Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives. Microbes and Infection, 8 (8). pp. 2245-2253. ISSN 1769-714X

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Abstract

p-Hydroxybenzoic acid derivatives (p-HBADs) are glycoconjugates secreted by all Mycobacterium tuberculosis isolates whose contribution to pathogenicity remains to be determined. The pathogenicity of three transposon mutants of M. tuberculosis deficient in the biosynthesis of some or all forms of p-HBADs was studied. Whilst the mutants grew similarly to the wild-type strain in macrophages and C57BL/6 mice, two of the mutants induced a more severe and diffuse inflammation in the lungs. The lack of production of some or all forms of p-HBADs in these two mutants also correlated with an increased secretion of the pro-inflammatory cytokines tumour-necrosis factor α, interleukin 6 and interleukin 12 in vivo. We propose that the loss of production of p-HBADs by tubercle bacilli results in their diminished ability to suppress the proinflammatory response to infection and that this ultimately provokes extensive pulmonary lesions in the C57BL/6 model of tuberculosis infection.

Item Type: Article
Keywords: Mycobacterium; Tuberculosis; Phenolic glycolipids; p-Hydroxybenzoic acid derivatives
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Molecular Medical Sciences > Bacteriology
Identification Number: https://doi.org/10.1016/j.micinf.2006.04.008
Depositing User: Griffin, Ruth
Date Deposited: 14 Dec 2017 15:26
Last Modified: 14 Dec 2017 15:32
URI: http://eprints.nottingham.ac.uk/id/eprint/48704

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