Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis - Evidence that this lipid is involved in the cell wall permeability barrier
Lr. Camacho et al., Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis - Evidence that this lipid is involved in the cell wall permeability barrier, J BIOL CHEM, 276(23), 2001, pp. 19845-19854
Among the few characterized genes that have products involved in the pathog
enicity of Mycobacterium tuberculosis, the etiological agent of tuberculosi
s, are those of the phthiocerol dimycocerosate (DIM) locus. Genes involved
in biosynthesis of these compounds are grouped on a 50-kilobase fragment of
the chromosome containing 13 genes. Analysis of mRNA produced from this 50
-kilobase fragment in the wild type strain showed that this region is subdi
vided into three transcriptional units. Biochemical characterization of fiv
e mutants with transposon insertions in this region demonstrated that (i) t
he complete DIM molecules are synthesized in the cytoplasm of M. tuberculos
is before being translocated into the cell wall; (ii) the genes fadD26 and
fadD28 are directly involved in their biosynthesis; and (iii) both the drrC
and mmpL7 genes are necessary for the proper localization of DIMs. Inserti
onal mutants unable to synthesize or translocate DIMs exhibit higher cell.
wall permeability and are more sensitive to detergent than the wild type st
rain, indicating for the first time that, in addition to being important vi
rulence factors, extractable lipids of M. tuberculosis play a role in the c
ell envelope architecture and permeability. This function may represent one
of the molecular mechanisms by which DIMs are involved in the virulence of
M. tuberculosis.