Lr. Camacho et al., Identification of a virulence gene cluster of Mycobacterium tuberculosis by signature-tagged transposon mutagenesis, MOL MICROB, 34(2), 1999, pp. 257-267
Tuberculosis remains the greatest cause of death worldwide due to a single
pathogen, In order to identify the genes required for the pathogenicity of
Mycobacterium tuberculosis, a functional genomic approach was developed. A
library of signature-tagged transposon mutants of this bacterium was constr
ucted and screened for those affected in their multiplication within the lu
ngs of mice. From 1927 mutants tested, 16 were attenuated for their virulen
ce. The insertions harboured by the selected mutants were mapped on the M.
tuberculosis genome and most of the mutated loci appeared to be involved in
lipid metabolism or transport across the membrane. Four independent mutati
ons identified a cluster of virulence genes located on a 50 kb chromosomal
region. These genes might be involved in the production of phthiocerol and
phenolphthiocerol derivatives, a group of molecules restricted to eight myc
obacterial species, seven of them being either strict or opportunistic path
ogens. The interaction of five mutant strains with mouse bone marrow macrop
hages was investigated. These five mutants were still able to multiply in t
his cell type, However, in three cases, there was a growth defect in compar
ison with the wild-type strain. The other two strains exhibited no clear di
fference from the virulent strain, MT103, in this model. This study, which
is the first global research of virulence factors of M. tuberculosis, opens
the way to a better understanding of the molecules that are key players in
the interaction of this pathogen with its host.