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. 2012;7(7):e37516.
doi: 10.1371/journal.pone.0037516. Epub 2012 Jul 19.

Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments

Christer Larsson  1 , Brian Luna, Nicole C Ammerman, Mamoudou Maiga, Nisheeth Agarwal, William R Bishai
Affiliations

Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments

Christer Larsson et al. PLoS One. 2012.

Abstract

The seven WhiB proteins of Mycobacterium tuberculosis (M.tb) are widely believed to be redox-sensing transcription factors due to their binding of iron-sulfur clusters and similarities to DNA binding proteins. Here, we explored the nature of this hypothesized relationship. We exposed M.tb to physiologic conditions such as gradual hypoxia, nitric oxide (NO), cyclic AMP and in vivo conditions, and measured transcription of the whiB genes. We found whiB3 to be induced both by hypoxia and NO, whiB7 to be induced in macrophage-like cells, and whiB4 to be induced in mouse lung. Cyclic AMP induced whiB1,-2, -4, -6 and -7. Our data indicate that the M.tb whiB genes are induced independently by various stimuli which may add versatility to their suggested redox-sensing properties.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Relative abundance of whiB1-7 transcripts.
mRNA levels of the seven M.tb whiB genes at mid-logarithmic growth in 7H9 presented as fold change in relation to sigA (set to 0). WhiB1 was highly expressed and whiB5 was under-expressed compared to the other whiB genes, which exhibited an expression level very close to that of sigA.
Figure 2
Figure 2. M.tb whiB1-7 expression in a self-generated oxygen depletion (Wayne) model.
Data are presented as fold-change compared to fully aerated (100% air saturation) cultures denoted as 0 on the y-axis. All genes were expressed in all conditions. whiB3 showed a consistent trend of upregulation starting at about 20% a.s. whiB2 showed a trend of slightly lower expression in low oxygen conditions although not reaching statistical significance at 10% and 0%+7days (p = 0.09 and 0.06 respectively) and with an apparent, non-significant upregulation at 3%.
Figure 3
Figure 3. Effect of nitric oxide on whiB1-7 expression.
M.tb CDC1551 was grown for 12 h in the presence of 500 µM DETA-NO. whiB3, whiB6 and to a lesser extent, whiB7 were upregulated.
Figure 4
Figure 4. Effect of db-cAMP on whiB1-7 expression.
M.tb CDC1551 was grown 24h in the presence of 500 µM db-cAMP. whiB1 and to a lesser extent −2 and −4 were up-regulated.
Figure 5
Figure 5. whiB1-7 expression in J774 macrophage-like cells and lungs of C3HeB/FeJ mice.
Expression levels compared to aerobic in vitro 7H9 growth. Only whiB6 and whiB7 were upregulated during J774 cell infection whereas whiB1, −4 and −7 were upregulated in the lungs of C3HeB/FeJ mice (5 weeks post-infection).
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