Table 1.
Comparison of regulation of expression of Mtb genes by nitrate respiration observed here and by physiologic situations or stresses as reported in the literature
| Condition | Regulation | Genes regulated by the indicated condition | Total no. that overlap (by chance) |
No. induced by nitrate respiration | No. repressed by nitrate respiration | Percent of total gene list that overlaps | Significance of the overlap, P value | |
| Iron depletion (39) (low iron culture: 2 μM FeCl3 vs. high iron culture: 50 μM FeCl3, H37Rv) | Induced | 66 | 14 | (2) | 13 | 1 | 11.67 | 4.17E-08 |
| Repressed | 27 | 2 | (1) | 0 | 2 | 1.67 | 2.05E-01 | |
| Hypoxia (22) (2 h at 0.2% oxygen, H37Rv) | Induced | 47 | 27 | (1) | 0 | 27 | 22.50 | <2.2e-16 |
| Enduring hypoxic response (62) (incubation at 0.2% oxygen over 4 d, H37Rv) | Induced | 230 | 17 | (7) | 12 | 5 | 14.17 | 6.53E-04 |
| Nitric oxide (23) (50 μM DETA/NO for 40 min, H37Rv) | Induced | 48 | 28 | (1) | 0 | 28 | 23.33 | <2.2e-16 |
| Hydrogen peroxide (41) (10 mM, 40 min, clinical isolate 1254) | Induced | 166 | 22 | (5) | 22 | 0 | 18.33 | 1.11E-08 |
| Repressed | 48 | 10 | (1) | 10 | 0 | 8.33 | 4.65E-06 | |
| pH 5.5 (40) (pH 5.5 vs. pH 7, H37Rv) | Induced | 261 | 16 | (8) | 15 | 1 | 13.33 | 5.72E-03 |
| Repressed | 375 | 18 | (11) | 1 | 17 | 15.00 | 3.27E-02 | |
| Intraphagosomal (42) (24 h, H37Rv) | Induced | 454 | 65 | (14) | 35 | 30 | 54.17 | <2.2e-16 |
| Induced, iNOS dependent | 60 | 32 | (2) | 9 | 23 | 26.67 | <2.2e-16 | |
| Repressed | 147 | 11 | (4) | 0 | 11 | 9.17 | 5.63E-03 | |
| Repressed, iNOS dependent | 8 | 3 | (1) | 0 | 3 | 2.50 | 3.31E-03 | |
| Intraphagosomal (40) (24 h, CDC 1551) | Induced | 266 | 32 | (8) | 9 | 23 | 26.67 | 2.39E-11 |
| Repressed | 111 | 1 | (3) | 0 | 1 | 0.83 | 9.65E-01 | |
| DNA damage (63) (induced by mitomycin C, H37Rv) | Induced | 113 | 1 | (3) | 1 | 0 | 0.83 | 9.67E-01 |
| Repressed | 26 | 2 | (1) | 2 | 0 | 1.67 | 1.94E-01 | |
| Starvation (64) (24 h after growth in PBS, H37Rv) | Induced | 252 | 6 | (8) | 6 | 0 | 5.00 | 7.69E-01 |
| Repressed | 301 | 12 | (9) | 6 | 6 | 10.00 | 1.94E-01 | |
| Nitrate respiration (Table S3) (genes regulated by nitrate respiration and no other physiologic stimuli reported above) | — | — | — | — | 6 | 5 | 10.83 | — |
The total number of genes induced or repressed by nitrate respiration is listed along with the total number reported to be regulated by the indicated condition. The number regulated in common is compared with the number that would be expected to show a similar regulation by chance calculated by a Fisher’s exact test. The columns labeled “No. induced/repressed by nitrate respiration” refer only to the number of overlapping genes. “Percent of total gene list that overlaps” indicates the percentage of all genes regulated by nitrate respiration that are also regulated by the condition of interest. The associated significance of this overlap, listed as a P value in the final column, was calculated using a Fisher’s exact test. Of note, genes regulated by mitomycin C-induced DNA damage and starvation did not significantly overlap with genes regulated by nitrate respiration. –, not applicable.