Table 3

Results for known and proposed targets in the targetTB pipeline

Target

Remarks

targetTB pipeline

A

B

C

E

F

G

H

I

J

K


I. Cell Wall Biosynthesis


DdlA (Rv2981c)

Known target of cycloserine [5]

X

X

EmbA (Rv3794)

Known target for ethambutol [7,75]

AftA (Rv3792)

Suggested as an attractive target [76]

X

X

AftB (Rv3805c)

Suggested as a potential target [77]

MurG (Rv2153c)

Suggested as a potential target [78]


II. Lipid Metabolism


FabH (Rv0533c)

Possible target of thiolactomycin; also suggested as potential target [79,80]

FabD (Rv2243)

Suggested as a potential target [81-83]

AcpM (Rv2244)

Induced on isoniazid treatment [81,84]

Pks13 (Rv3800c)

Suggested as a promising target against Corynebacterineae [85]

InhA (Rv1484)

Known target for isoniazid, ethionamide [4]

PcaA (Rv0470c)

Suggested as a possible target of thiacetazone [86]

MmaA1 (Rv0645c)

-do-

FadD32 (Rv3801c)

Suggested as a promising target [87]

DesA3 (Rv3229c)

Suggested as a possible target [88]

?

X

Fas (Rv2524c)

Possible target of pyrazinamide [89]


III. Intermediary Metabolism and Respiration


LysA (Rv1293)

Lysine auxotroph has vaccine potential [90]; suggested as potential target [91]

TrpD (Rv2192c)

-do-

X

X

LeuA (Rv3710)

Suggested as potential target [92]

DapB (Rv2773c)

Suggested as potential target [93]

X

X

X

AroB (Rv2538c)

Shikimate pathway suggested as an attractive target [94]

ArgA (Rv2747)

Essential enzyme catalysing initial step of arginine biosynthesis [95]

AlrA (Rv3423c)

Known target of Cycloserine [5]

X

X

DfrA (Rv2763c)

Important drug target in many pathogens [96]. Suggested as drug target in [96,97]

X

-

X

PanB (Rv2225)

Critical for pantothenic acid synthesis [98]

PanC (Rv3602c)

Critical for pantothenic acid synthesis [98]; suggested as potential target [99]

PanD (Rv3601c)

Critical for pantothenic acid synthesis [98]; suggested as potential target [100]

X

X

PanK (Rv1092c)/CoaA

Prokaryotic enzymes involved in the synthesis of CoA are good targets [101]; [102]

CysH (Rv2392)

Suggested as an attractive drug target [103-106]; CysH is important for Mtb protein during latent infection [58]

IspD (Rv3582c)

Potential drug target [107]

IspF (Rv3581c)

Potential drug target [107]; attractive target in many pathogens [59]

Icl (Rv0467)

Required for persistence of Mtb in macrophages and mice [36]; suggested as an attractive target [57]. Icl1 and Icl2 are required for fatty acid catabolism and virulence in Mtb [108]

X

X

AtpE1 (Rv1305)

Inhibited by a diarylquinoline drug R207910 in vitro [109]

Cyp121 (Rv2276)

Putative essential gene. Possible role in virulence through studies with ΔAraC/XylS gene regulator mutant (ΔRv1931c) [110]. Induced in isoniazid- and thiolactomycin-treated Mtb [111]


IV. Information Pathways


GyrA (Rv0006)

Known target of uoroquinolones [112,113]

X

-

X

X

GyrB (Rv0005)

-do-

X

X

X

RpoB (Rv0667)

Known target of rifampicin [8]

X

X

RpsL (Rv0683)

Known target of Streptomycin [114]

X

-

X

X


V. Regulatory proteins


GlnE (Rv2221c)

Essential for growth of Mtb [115]

MtrA (Rv3246c)

Essential for growth of Mtb [116]

X

-

X

DevR (Rv3133c)

Two-component system is a novel target in dormant mycobacteria [117]; essential for growth of Mtb under conditions of low oxygen [118]

X

X

DevS (Rv3132c)

Two-component system is a novel target in dormant mycobacteria [117]; part of the DevR-DevS two-component signal transduction system [118,119]

PknB (Rv0014c)

Possibly essential for mycobacterial growth and hence possible target [53]

X

X

PknG (Rv0410c)

Crucial virulence factor [120]; possibly essential for mycobacterial growth and hence possible targets [53]

X

X

X

MbtA (Rv2384)

An important adenylation enzyme required for siderophore biosynthesis [121]

X

X

IdeR (Rv2711)

Suggested as target [122,123]

X

-

X

X


An account of the passage of known targets (previously reported in literature) through the targetTB pipeline. The putative targets are classified based on their broad functional categories. A, B, C, E, F, G, H, I, J and K refer to the different filters depicted in Fig. 1 and described in the text. '✔' indicates that the given protein passes the filter, while a 'X' indicates a failure. A '?' indicates that the analysis was not performed due to lack of appropriate data, while '-' indicates that the protein was not passed through the filter due to failure at a previous stage. All proteins in the H-List indicated in Fig. 3 would have a '✔' at levels A-H. '●' indicates the additional lists (I/J/K) in which a target from the H-List is present.

Raman et al. BMC Systems Biology 2008 2:109   doi:10.1186/1752-0509-2-109

Open Data