title: Comparative investigation of the pathogenicity of three Mycobacterium tuberculosis mutants defective in the synthesis of p-hydroxybenzoic acid derivatives.
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 alpha, 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.
authors.affiliation: Unité de Génétique Mycobactérienne, Institut Pasteur, Paris, France.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Stadthagen
authors.forename: Mary
authors.initials: M
authors.lastname: Jackson
authors.forename: Patricia
authors.initials: P
authors.lastname: Charles
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boudou
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barilone
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Patricia
authors.initials: P
authors.lastname: Constant
authors.forename: Avraham
authors.initials: A
authors.lastname: Liav
authors.forename: Iveta
authors.initials: I
authors.lastname: Bottova
authors.forename: Jérôme
authors.initials: J
authors.lastname: Nigou
authors.forename: Thérèse
authors.initials: T
authors.lastname: Brando
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.forename: Mamadou
authors.initials: M
authors.lastname: Daffé
authors.forename: Pearline
authors.initials: P
authors.lastname: Benjamin
authors.forename: Stephen
authors.initials: S
authors.lastname: Coade
authors.forename: Roger S
authors.initials: RS
authors.lastname: Buxton
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Tascon
authors.forename: Aaron
authors.initials: A
authors.lastname: Rae
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robertson
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Lowrie
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.forename: Brigitte
authors.initials: B
authors.lastname: Gicquel
authors.forename: Ruth
authors.initials: R
authors.lastname: Griffin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D004251:DNA Transposable Elements; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D010226:Parabens / Q000378:metabolism*; D014376:Tuberculosis / Q000382:microbiology
chemical_list: D016207:Cytokines; D004251:DNA Transposable Elements; D010226:Parabens; C038193:4-hydroxybenzoic acid