Table 3 Results for known and proposed targets in the targetTB pipeline

I. Cell Wall Biosynthesis

Known target of cycloserine [5]

✔

✔

X

✔

✔

✔

X

Known target for ethambutol [7, 75]

✔

✔

✔

✔

✔

✔

✔

Suggested as an attractive target [76]

✔

✔

X

✔

✔

✔

X

Suggested as a potential target [77]

✔

✔

✔

✔

✔

✔

✔

Suggested as a potential target [78]

✔

✔

✔

✔

✔

✔

✔

●

●

II. Lipid Metabolism

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

✔

✔

✔

✔

✔

✔

✔

●

Suggested as a potential target [81–83]

✔

✔

✔

✔

✔

✔

✔

●

Induced on isoniazid treatment [81, 84]

✔

✔

✔

✔

✔

✔

✔

●

Suggested as a promising target against Corynebacterineae [85]

✔

✔

✔

✔

✔

✔

✔

●

Known target for isoniazid, ethionamide [4]

✔

✔

✔

✔

✔

✔

✔

●

Suggested as a possible target of thiacetazone [86]

✔

✔

✔

✔

✔

✔

✔

●

-do-

✔

✔

✔

✔

✔

✔

✔

●

●

Suggested as a promising target [87]

✔

✔

✔

✔

✔

✔

✔

●

●

Suggested as a possible target [88]

✔

✔

?

✔

✔

✔

X

Possible target of pyrazinamide [89]

✔

✔

✔

✔

✔

✔

✔

III. Intermediary Metabolism and Respiration

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

✔

✔

✔

✔

✔

✔

✔

●

-do-

✔

✔

✔

X

✔

✔

X

Suggested as potential target [92]

✔

✔

✔

✔

✔

✔

✔

●

Suggested as potential target [93]

✔

✔

✔

X

✔

X

X

Shikimate pathway suggested as an attractive target [94]

✔

✔

✔

✔

✔

✔

✔

●

●

Essential enzyme catalysing initial step of arginine biosynthesis [95]

✔

✔

✔

✔

✔

✔

✔

Known target of Cycloserine [5]

✔

✔

X

✔

✔

✔

X

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

✔

X

-

✔

✔

✔

X

Critical for pantothenic acid synthesis [98]

✔

✔

✔

✔

✔

✔

✔

●

●

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

✔

✔

✔

✔

✔

✔

✔

●

●

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

✔

✔

X

✔

✔

✔

X

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

✔

✔

✔

✔

✔

✔

✔

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

✔

✔

✔

✔

✔

✔

✔

●

Potential drug target [107]

✔

✔

✔

✔

✔

✔

✔

●

●

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

✔

✔

✔

✔

✔

✔

✔

●

●

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

Inhibited by a diarylquinoline drug R207910 in vitro [109]

✔

✔

✔

✔

✔

✔

✔

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

Known target of uoroquinolones [112, 113]

X

✔

-

✔

✔

X

X

-do-

✔

✔

X

✔

✔

X

X

Known target of rifampicin [8]

✔

✔

✔

✔

✔

X

X

Known target of Streptomycin [114]

✔

X

-

✔

✔

X

X

V. Regulatory proteins

Essential for growth of Mtb [115]

✔

✔

✔

✔

✔

✔

✔

Essential for growth of Mtb [116]

X

✔

-

✔

✔

✔

X

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

✔

✔

✔

X

✔

✔

X

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

✔

✔

✔

✔

✔

✔

✔

●

●

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

✔

✔

✔

✔

X

✔

X

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

✔

✔

X

X

✔

✔

X

An important adenylation enzyme required for siderophore biosynthesis [121]

✔

✔

X

✔

✔

✔

X

Suggested as target [122, 123]

X

✔

-

✔

✔

X

X