In:
Infection and Immunity, American Society for Microbiology, Vol. 72, No. 3 ( 2004-03), p. 1733-1745
Kurzfassung:
The Mycobacterium tuberculosis alternate sigma factor, SigF, is
expressed during stationary growth phase and under stress conditions in vitro. To better understand the function of SigF we studied the
phenotype of the M. tuberculosis Δ sigF mutant
in vivo during mouse infection, tested the mutant as a vaccine in rabbits, and evaluated the mutant's microarray expression profile
in comparison with the wild type. In mice the growth rates of theΔ sigF mutant and wild-type strains were nearly
identical during the first 8 weeks after infection. At 8 weeks, theΔ sigF mutant persisted in the lung, while the wild
type continued growing through 20 weeks. Histopathological analysis showed that both wild-type and mutant strains had similar degrees of
interstitial and granulomatous inflammation during the first 12 weeks of infection. However, from 12 to 20 weeks the mutant strain showed
smaller and fewer lesions and less inflammation in the lungs and spleen. Intradermal vaccination of rabbits with the M.
tuberculosis Δ sigF strain, followed by aerosol
challenge, resulted in fewer tubercles than did intradermal M.
bovis BCG vaccination. Complete genomic microarray analysis
revealed that 187 genes were relatively underexpressed in the absence of SigF in early stationary phase, 277 in late stationary phase, and
only 38 genes in exponential growth phase. Numerous regulatory genes and those involved in cell envelope synthesis were down-regulated in
the absence of SigF; moreover, the Δ sigF mutant strain
lacked neutral red staining, suggesting a reduction in the expression of envelope-associated sulfolipids. Examination of
5′-untranslated sequences among the downregulated genes revealed multiple instances of a putative SigF consensus recognition
sequence: GGTTTCX 18 GGGTAT.
These results indicate that in the mouse the M.
tuberculosis Δ sigF mutant strain persists in the
lung but at lower bacterial burdens than wild type and is attenuated by histopathologic assessment. Microarray analysis has identified
SigF-dependent genes and a putative SigF consensus recognition site.
Materialart:
Online-Ressource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.72.3.1733-1745.2004
Sprache:
Englisch
Verlag:
American Society for Microbiology
Publikationsdatum:
2004
ZDB Id:
1483247-1
