Research Repository

See what's under the surface

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; Boudoua, Frédéric; Barilonea, Nathalie; Huerree, Michel; Constant, Patricia; Liav, Avraham; Bottova, Iveta; Nigou, Jérome; Brandod, Thérèse; Puzo, Germain; Daffé, Mamadou; Benjamin, Pearline; Coade, Stephen; Buxton, Roger S.; Tascon, Ricardo E.; Rae, Aaron; Robertson, Brian D.; Lowrie, Douglas B.; Young, Douglas B.; Gicquel, Brigitte; Griffin, R.

Authors

Gustavo Stadthagen

Mary Jackson

Patricia Charles

Frédéric Boudoua

Nathalie Barilonea

Michel Huerree

Patricia Constant

Avraham Liav

Iveta Bottova

Jérome Nigou

Thérèse Brandod

Germain Puzo

Mamadou Daffé

Pearline Benjamin

Stephen Coade

Roger S. Buxton

Ricardo E. Tascon

Aaron Rae

Brian D. Robertson

Douglas B. Lowrie

Douglas B. Young

Brigitte Gicquel

R. Griffin mbzrg@nottingham.ac.u,

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.

Journal Article Type Article
Journal Microbes and Infection
Print ISSN 1286-4579
Electronic ISSN 1769-714X
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 8
Issue 8
Institution Citation Stadthagen, G., Jackson, M., Charles, P., Boudoua, F., Barilonea, N., Huerree, M., …Griffin, R. (in press). Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives. Microbes and Infection, 8(8), doi:10.1016/j.micinf.2006.04.008
DOI https://doi.org/10.1016/j.micinf.2006.04.008
Keywords Mycobacterium; Tuberculosis; Phenolic glycolipids; p-Hydroxybenzoic acid derivatives
Publisher URL http://www.sciencedirect.com/science/article/pii/S1286457906001705?via%3Dihub#
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Downloadable Citations