TABLE 1.
List of the 14 DD M. tuberculosis candidate genes chosen for this study that in a prior report (20) were found downregulated or upregulated in expression in the PBS-RIF model in comparison to PBS-DMSO controls
DD M. tuberculosis candidate gene | Gene product/functiong | Functional category | Avg fold Δexpression PBS-RIF DD M. tuberculosisa,b | Avg fold Δexpression −K+ RIF DD M. tuberculosisc | Implicated in models of M. tuberculosis persistence?d | Avg CT (day 0 pooled sputum)e | Ranked expression 0–100 (day 0 sputum)f |
---|---|---|---|---|---|---|---|
Downregulated | |||||||
icl1 (Rv0467) | Isocitrate lyase/involved in glyoxylate bypass in TCA cycle | Intermediary metabolism and respiration | −45.9h | −3.0 | Yes | 20.1 | 99.6 |
carD (Rv3583c) | RNA-Pol binding transcription factor | Regulatory proteins (transcriptional) | −22.0h | −1.4 | 21.4 | 99.2 | |
vapB10 (Rv1398c) | Possible antitoxin | Virulence, detoxification, adaptation | −29.4h | −2.5 | Yes | 20.8 | 99.2 |
ppsA (Rv2931) | Phenol phthiocerol synthesis type I polyketide synthase | Lipid metabolism | −13.9h | −1.8 | Yes | 21.4 | 95.5 |
hspX (Rv2031c) | Heat shock protein (α-crystallin homolog) | Virulence, detoxification, adaptation | −10.5 | 1.0 | Yes | 20.4 | 92.3 |
Rv1738 | Similar to bacterial hibernation factors | Conserved hypotheticals | −13.8 | 6.0 | Yes | 21.9 | 98.5 |
tatA (Rv2094c) | Sec-independent protein translocase | Cell wall and cell processes | −14.0 | −9.7 | 20.6 | 98.1 | |
whiB1 (Rv3219) | NO-responsive transcription factor | Regulatory proteins (transcriptional) | −11.3h | −4.2 | Yes | 24.0 | 98.6 |
pks15 (Rv2947c) | Probable polyketide synthase | Lipid metabolism | −16.0h | 2.6 | 25.5 | 60 | |
lldD2 (Rv1872c) | Possible l-lactate dehydrogenase (cytochrome) | Intermediary metabolism and respiration | −10.0h | −3.6 | Yes | 24.0 | 95.1 |
Upregulated | |||||||
arsC (Rv2643) | Probable arsenic-transport integral membrane protein | Cell wall and cell processes | 7.7 | 2.6 | Yes | 25.2 | 56.5 |
lpqX (Rv1228) | Probable lipoprotein | Cell wall and cell processes | 17.2h | 8.4 | 27.1 | 72.8 | |
ugpC (Rv2832c) | Probable sn-glycerol-3-phosphate transport ABC transporter | Cell wall and cell processes | 11.6h | 9.6 | 25.7 | 32.3 | |
rpfE (Rv2450c) | Probable resuscitation-promoting factor | Cell wall and cell processes | 11.2 | −2.3 | 27.1 | 32.3 |
Comparing DD M. tuberculosis positive versus negative cultures from Saito et al. (20).
The PBS used in this model contains potassium.
Comparing DD M. tuberculosis positive versus negative cultures from Ignatov et al. (22).
Torrey et al. (23).
This study.
Walter et al. (21) (100 represents highest expressed gene in sputum based on high-throughput qRT-PCR).
Abbreviations: TCA, tricarboxylic acid cycle; Pol, polymerase; NO, nitric oxide; ABC, ATP-binding cassette.
Other putative gene/operon family members show similar changes in expression.