Table 2.
List of prioritized protein targets considering gene essentiality, pathogenic Kp scope and metabolic network metrics (ranked according to equation (1)).
| Rank | Locus number^ | Gene | Product | Product size (aa) | Structural druggability* | Essential | Choke-point | Network centrality | Presence in pathogenic Kp (%) | Pathways involved# | DrugBank Inhibitor& |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 01032 | fabB | 3-oxoacyl-[acyl-carrier-protein] synthase 1 | 407 | 0.74 | Yes | Yes | 0.64 | 100.0 | Biotin [B], Fatty acids [B] | Approved (DB01034) |
| 2 | 02296 | argA | Amino-acid acetyltransferase | 443 | 0.75 | Yes | Yes | 0 | 100.0 | L-arginine [B] | ND |
| 3 | 01798 | lpxA | UDP-N-acetylglucosamine O-acyltransferase | 263 | 0.88 | Yes | Yes | 0.29 | 100.0 | Lipopolysaccharide [B] | Experimental (DB08558) |
| 4 | 01899 | lpxC | UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase | 306 | 0.78 | Yes | Yes | 0.29 | 100.0 | Lipopolysaccharide [B] | Experimental (DB07861) |
| 5 | 04921 | fabH | 3-oxoacyl-[acyl-carrier-protein] synthase 3 | 318 | 0.77 | No | Yes | 0.64 | 100.0 | Biotin [B], Fatty acids [B] | Approved (DB01034) Cerulenin |
| 6 | 01814 | dapD | 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase | 274 | 0.96 | Yes | Yes | 0.08 | 100.0 | L-lysine [B] | Experimental (DB01856) |
| 7 | 01909 | murF | UDP-N-acetylmuramoyl-tripeptide–D-alanyl-D-alanine ligase | 452 | 0.75 | Yes | Yes | 0.08 | 100.0 | Peptidoglycan [B] | Experimental (DB06970) |
| 8 | 03831 | dapE | succinyl-diaminopimelate desuccinylase | 375 | 0.81 | Yes | Yes | 0.08 | 100.0 | L-lysine [B] | ND |
| 9 | 01800 | lpxD | UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase | 341 | 0.82 | Yes | Yes | 0.07 | 100.0 | Lipopolysaccharide [B] | ND |
| 10 | 05433 | fabI | Enoyl-[acyl-carrier-protein] reductase [NADH] | 262 | 0.72 | Yes | Yes | 0.06 | 100.0 | Biotin [B], Fatty acids [B] | Approved (DB08604) Triclosan |
| 11 | 01797 | lpxB | Lipid-A-disaccharide synthase | 383 | 0.92 | Yes | Yes | 0.06 | 100.0 | Lipopolysaccharide [B] | ND |
| 12 | 01905 | murG | undecaprenyl-PP-MurNAc-pentapeptide-UDPGlcNAc GlcNAc transferase | 356 | 0.80 | Yes | Yes | 0.06 | 100.0 | Peptidoglycan [B] | Murgocil (Ref.106) |
| 13 | 00662 | asd | Aspartate-semialdehyde dehydrogenase | 368 | 0.58 | Yes | Yes | 0.05 | 100.0 | L-lysine [B], L-threonine [B], L-methionine [B], L-homoserine [B] | Experimental (DB03502) |
| 14 | 04866 | purB | Adenylosuccinate lyase | 456 | 0.84 | Yes | Yes | 0.05 | 100.0 | Purine nucleotides [B] | ND |
| 15 | 04914 | tmk | Thymidylate kinase | 213 | 0.58 | Yes | Yes | 0.05 | 100.0 | Pyrimidine deoxyribonucleotides [B] | Experimental (DB03280) |
^The K. pneumoniae Kp13 locus suffix ‘KP13_’ is omitted; *druggability of the protein considering the highest scoring pocket. #B: biosynthesis. &Data gathered from http://www.drugbank.ca for orthologs of each protein with relevance studied on a per-target basis. ND, not determined.