| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T33193 | ||||
| Target Name | Penicillin binding protein 3 | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Cefotiam | Drug Info | IC50 = 105 ng/mL | [553170] | |
| Cefmetazole | Drug Info | IC50 = 109 ng/mL | [552547] | ||
| Mezlocillin | Drug Info | IC50 = 125 ng/mL | [552205] | ||
| Aztreonam | Drug Info | IC50 = 8000 ng/mL | [552205] | ||
| Cefmenoxime | Drug Info | IC50 = 80 ng/mL | [553170] | ||
| Action against Disease Model | Latamoxef | Reduced cell permeability and target penicillin-binding protein modification were investigated as mechanisms of intrinsic resistance in strains of Pseudomonas aeruginosa resistant to carbenicillin (MIC greater than 128 mg/L) independently of beta-lactamase production. The carbenicillin-resistant strains were also remarkably resistant to other beta-lactams, quinolones, tetracyline and chloramphenicol, whereas carbenicillin-hypersusceptible strains (MIC less than 2 mg/L) were very sensitive to these antimicrobial compounds. These observations suggested a non-specific mechanism of resistance involving reduced permeability of the outer layers of the bacterial cell. However, carbenicillin-resistant and carbenicillin-sensitive strains had identical porin levels and the target penicillin-binding proteins of carbenicillin-resistant (MIC 256-2048 mg/L), carbenicillin-sensitive (MIC 64 mg/L) and carbenicillin-hypersusceptible (MIC 0.015 mg/L) strains were equally sensitiveto beta-lactams. Thus, subtle changes in porin function or additional outer-membrane barriers regulating permeability may be involved in intrinsic resistance.IC50: 60 ng/mL | [553155] | Drug Info | |
| Aztreonam | Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectr uM gram-negative activity observed with doripenem. | [552781] | Drug Info | ||
| References | |||||
| Ref 553170 | Cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities. Antimicrob Agents Chemother. 1981 Jan;19(1):56-65. | ||||
| Ref 553155 | Penicillin-binding proteins, porins and outer-membrane permeability of carbenicillin-resistant and -susceptible strains of Pseudomonas aeruginosa. J Med Microbiol. 1984 Oct;18(2):261-70. | ||||
| Ref 552781 | Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2008 Apr;52(4):1510-2. doi: 10.1128/AAC.01529-07. Epub 2008 Feb 4. | ||||
| Ref 552547 | Neutrophil-anti-microbial interaction in the established infection: effect on Staphylococcus aureus. J Infect. 2006 May;52(5):320-8. Epub 2005 Sep 19. | ||||
| Ref 552205 | Competition of various beta-lactam antibiotics for the major penicillin-binding proteins of Helicobacter pylori: antibacterial activity and effects on bacterial morphology. Antimicrob Agents Chemother. 1999 Nov;43(11):2702-9. | ||||
| Ref 552205 | Competition of various beta-lactam antibiotics for the major penicillin-binding proteins of Helicobacter pylori: antibacterial activity and effects on bacterial morphology. Antimicrob Agents Chemother. 1999 Nov;43(11):2702-9. | ||||
| Ref 553170 | Cefmenoxime (SCE-1365), a novel broad-spectrum cephalosporin: in vitro and in vivo antibacterial activities. Antimicrob Agents Chemother. 1981 Jan;19(1):56-65. | ||||
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