Abbreviated Journal Title
J. Bacteriol.
Keywords
TUBERCLE BACILLUS; TRANSPOSON MUTAGENESIS; VIRULENT-STRAINS; FATTY-ACIDS; GUINEA-PIGS; BIOSYNTHESIS; GENES; MICE; IDENTIFICATION; TRANSCRIPTION; Microbiology
Abstract
Similarities between Mycobacterium tuberculosis phoP-phoR mutants and the attenuated laboratory strain M. tuberculosis H37Ra in terms of morphological and cytochemical properties, lipid content, gene expression and virulence attenuation prompted us to analyze the functionality of this two-component regulator in the latter strain. Sequence analysis revealed a base substitution resulting in a one-amino-acid change in the likely DNA-binding region of PhoP in H37Ra relative to H37Rv. Using gel-shift assays, we show that this mutation abrogates the ability of the H37Ra PhoP protein to bind to a 40-bp segment of its own promoter. Consistent with this result, the phoP gene from H37Rv but not that from H37Ra was able to restore the synthesis of sulfolipids, diacyltrehaloses and polyacyltrehaloses in an isogenic phoP-phoR knock-out mutant of M. tuberculosis Moreover, complementation of H37Ra with phoP from H37Rv fully restored sulfolipid, diacyltrehalose and polyacyltrehalose synthesis, clearly indicating that the lack of production of these lipids in H37Ra is solely due to the point mutation in phoP. Using a pks2-3/4 knock-out mutant of M. tuberculosis H37Rv, evidence is further provided that the above-mentioned polyketide-derived acyltrehaloses do not significantly contribute to the virulence of the tubercle bacillus in a mouse model of infection. Reasons for the attenuation of H37Ra thus most likely stand in other virulence factors, many of which are expected to belong to the PhoP regulon and another of which, unrelated to PhoP, appears to be the lack of production of phthiocerol dimycocerosates in this strain.
Journal Title
Journal of Bacteriology
Volume
190
Issue/Number
4
Publication Date
1-1-2008
Document Type
Article
Language
English
First Page
1329
Last Page
1334
WOS Identifier
ISSN
0021-9193
Recommended Citation
Chesne-Seck, Marie-Laure; Barilone, Nathalie; Boudou, Frédéric; Asensio, Jesús Gonzalo; Kolattukudy, Pappachan E.; Martín, Carlos; Cole, Stewart T.; Gicquel, Brigitte; Gopaul, Deshmukh N.; and Jackson, Mary, "A point mutation in the two-component regulator PhoP-PhoR accounts for the absence of polyketide-derived acyltrehaloses but not that of phthiocerol dimycocerosates in Mycobacterium tuberculosis H37Ra" (2008). Faculty Bibliography 2000s. 220.
https://stars.library.ucf.edu/facultybib2000/220
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