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

Stadthagen, Gustavo, Jackson, Mary, Charles, Patricia, Boudou, Frederic, Barilone, Nathalie, Huerre, Michel, Constant, Patricia, Liav, Avraham, Bottova, Iveta, Nigou, Jerome, Brando, Therese, Puzo, Germain, Daffe, Mamadou, Benjamin, Pearline, Coade, Stephen, Buxton, Roger S., Tascon, Ricardo E., Rae, Aaron, Robertson, Brian D., Lowrie, Douglas B., Young, Douglas B., Gicquel, Brigitte and Griffin, Ruth (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 (print) 1286-4579

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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 pro-inflammatory response to infection and that this ultimately provokes extensive pulmonary lesions in the C57BL/6 model of tuberculosis infection.

Item Type: Article
Additional Information: This work was supported by the European Commission, within the 5th and 6th Framework contract numbers; QLK2-CT-1999-01093 and LSHP-CT-2003-503367, the CONACyT fellowship no. 175523 from Mexico, the National Institutes of Health grant RO1 AI064798-01, the Marie Curie Training Site program no. CT-2000-00058 from the European Commission, the Medical Research Council and the Wellcome Trust and the Burroughs Wellcome Foundation, reference number 059125/Z/99/A.
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science (until 2011)
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Depositing User: Ruth Griffin
Date Deposited: 07 Apr 2017 11:34
Last Modified: 07 Apr 2017 11:34
DOI: https://doi.org/10.1016/j.micinf.2006.04.008
URI: http://eprints.kingston.ac.uk/id/eprint/33833

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