Table 3.
List of prioritized protein targets by incorporating protein overexpression in PB exposure (ranked according to equation (2)).
| 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 | 0.76 | Yes | Yes | 0.64 | 100.0 | Biotin [B], Fatty acids [B] | Approved (DB01034) |
| 2 | 01798 | lpxA | UDP-N-acetylglucosamine O-acyltransferase | 263 | 0.88 | Yes | Yes | 0.29 | 100.0 | Lipopolysaccharide [B] | Experimental (DB08558) |
| 3 | 01899 | lpxC | UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase | 306 | 0.78 | Yes | Yes | 0.29 | 100.0 | Lipopolysaccharide [B] | Experimental (DB07861) |
| 4 | 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) |
| 5 | 01800 | lpxD | UDP-3-O-[3-hydroxymyristoyl] glucosamine N-acyltransferase | 341 | 0.82 | Yes | Yes | 0.07 | 100.0 | Lipopolysaccharide [B] | ND |
| 6 | 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) |
| 7 | 03824 | dapA | Dihydrodipicolinate synthase | 292 | 0.81 | Yes | Yes | 0.03 | 100.0 | L-lysine [B] | Experimental (DB02370) |
| 8 | 01459 | kdsA | 2-dehydro-3-deoxyphosphooctonate aldolase | 284 | 0.71 | Yes | Yes | 0.03 | 100.0 | 3-deoxy-D-manno-octulosonate [B], lipopolysaccharide [B] | Experimental (DB02433) |
| 9 | 00796 | pssA | CDP-diacylglycerol–serine O-phosphatidyltransferase | 451 | 0.86 | Yes | Yes | 0.06 | 97 | Phosphatidylethanolamine [B] | ND |
| 10 | 01108 | glmM | Phosphoglucosamine mutase | 445 | 0.54 | Yes | Yes | 0.01 | 100.0 | UDP-N-acetyl glucosamine [B] | ND |
| 11 | 31485 | fabD | Malonyl CoA-acyl carrier protein transacylase | 309 | 0.70 | Yes | Yes | 0.0 | 100.0 | Fatty acids [B] | ND |
| 12 | 00029 | glmS | Glucosamine–fructose-6-phosphate aminotransferase isomerizing | 609 | 0.91 | Yes | Yes | 1.0 | 100.0 | UDP-N-acetyl-D-glucosamine [B], O-antigen [B] | Experimental (DB02445) |
| 13 | 04702 | galU | UTP–glucose-1-phosphate uridylyltransferase | 300 | 0.57 | Yes | Yes | 0.17 | 100.0 | UDP-glucose [B] | ND |
| 14 | 01466 | ispE | 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase | 283 | 0.55 | Yes | Yes | 0.12 | 100.0 | Isoprenoid [B] | Experimental (DB03687) |
| 15 | 03868 | fabA | 3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase | 188 | 0.93 | Yes | Yes | 0.10 | 100.0 | Biotin [B], Fatty acids [B] | Experimental (DB03813) |
^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.