scholarly journals Affinity of Tomopenem (CS-023) for Penicillin-Binding Proteins in Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa

2008 ◽  
Vol 53 (3) ◽  
pp. 1238-1241 ◽  
Author(s):  
Tetsufumi Koga ◽  
Chika Sugihara ◽  
Masayo Kakuta ◽  
Nobuhisa Masuda ◽  
Eiko Namba ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Binding Proteins ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Penicillin Binding Proteins ◽  
E Coli ◽  
High Affinity

ABSTRACT Tomopenem (formerly CS-023), a novel 1β-methylcarbapenem, exhibited high affinity for penicillin-binding protein (PBP) 2 in Staphylococcus aureus, PBP 2 in Escherichia coli, and PBPs 2 and 3 in Pseudomonas aeruginosa, which are considered major lethal targets. Morphologically, tomopenem induced spherical forms in E. coli and short filamentation with bulges in P. aeruginosa, which correlated with the drug's PBP profiles. The potential of resistance of these bacteria to tomopenem was comparable to that to imipenem.

scholarly journals Affinity of Doripenem and Comparators to Penicillin-Binding Proteins in Escherichia coli and Pseudomonas aeruginosa

2008 ◽  
Vol 52 (4) ◽  
pp. 1510-1512 ◽  
Author(s):  
Todd A. Davies ◽  
Wenchi Shang ◽  
Karen Bush ◽  
Robert K. Flamm
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Cell Death ◽  
Broad Spectrum ◽  
Binding Proteins ◽  
Penicillin Binding Protein ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
High Affinity ◽  
Affinity Profile

ABSTRACT 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-spectrum gram-negative activity observed with doripenem.

scholarly journals The ponA Gene of Enterococcus faecalis JH2-2 Codes for a Low-Affinity Class A Penicillin-Binding Protein

2004 ◽  
Vol 186 (13) ◽  
pp. 4412-4416 ◽  
Author(s):  
Colette Duez ◽  
Séverine Hallut ◽  
Noureddine Rhazi ◽  
Séverine Hubert ◽  
Ana Amoroso ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Enterococcus Faecalis ◽  
Binding Proteins ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Penicillin Binding Proteins ◽  
Class A ◽  
Lipid Ii

ABSTRACT A soluble derivative of the Enterococcus faecalis JH2-2 class A PBP1 (*PBP1) was overproduced and purified. It exhibited a glycosyltransferase activity on the Escherichia coli 14C-labeled lipid II precursor. As a dd- peptidase, it could hydrolyze thiolester substrates with efficiencies similar to those of other class A penicillin-binding proteins (PBPs) and bind β-lactams, but with k 2/K (a parameter accounting for the acylation step efficiency) values characteristic of penicillin-resistant PBPs.

scholarly journals Binding of Ceftobiprole and Comparators to the Penicillin-Binding Proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae

2007 ◽  
Vol 51 (7) ◽  
pp. 2621-2624 ◽  
Author(s):  
Todd A. Davies ◽  
Malcolm G. P. Page ◽  
Wenchi Shang ◽  
Ted Andrew ◽  
Malgosia Kania ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Streptococcus Pneumoniae ◽  
Binding Proteins ◽  
Tight Binding ◽  
Gram Negative ◽  
Penicillin Binding Proteins ◽  
Gram Positive Bacteria

ABSTRACT Ceftobiprole exhibited tight binding to PBP2a in methicillin-resistant Staphylococcus aureus, PBP2x in penicillin-resistant Streptococcus pneumoniae, and PBP3 and other essential penicillin-binding proteins in methicillin-susceptible S. aureus, Escherichia coli, and Pseudomonas aeruginosa. Ceftobiprole also bound well to PBP2 in the latter organisms, contributing to the broad-spectrum antibacterial activity against gram-negative and gram-positive bacteria.

scholarly journals Affinity of the New Cephalosporin CXA-101 to Penicillin-Binding Proteins of Pseudomonas aeruginosa

2010 ◽  
Vol 54 (9) ◽  
pp. 3933-3937 ◽  
Author(s):  
Bartolomé Moyá ◽  
Laura Zamorano ◽  
Carlos Juan ◽  
Yigong Ge ◽  
Antonio Oliver
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bactericidal Activity ◽  
Cell Morphology ◽  
Binding Proteins ◽  
Bacterial Load ◽  
Penicillin Binding Protein ◽  
Lower Affinity ◽  
Penicillin Binding Proteins ◽  
Log Reduction ◽  
High Affinity

ABSTRACT CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. The objective of this study was to determine the penicillin-binding protein (PBP) inhibition profile of CXA-101 compared to that of ceftazidime (PBP3 inhibitor) and imipenem (PBP2 inhibitor). Killing kinetics, the induction of AmpC expression, and associated changes on cell morphology were also investigated. The MICs for CXA-101, ceftazidime, and imipenem were 0.5, 1, and 1 μg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1× the MIC (0.5 μg/ml) producing a >3-log reduction in bacterial load after 8 h of incubation. Live-dead staining showed that concentrations of CXA-101 as low as 0.5× the MIC stopped bacterial septation and induced an intense filamentation, which is consistent with the documented high affinity of PBP3. CXA-101 was found to be a potent PBP3 inhibitor and showed affinities ≥2-fold higher than those of ceftazidime for all of the essential PBPs (1b, 1c, 2, and 3). Compared to imipenem, in addition to the obvious inverse PBP2/PBP3 affinities, CXA-101 showed a significantly higher affinity for PBP1b but a lower affinity for PBP1c. Furthermore, CXA-101, like ceftazidime and in contrast to imipenem, was found to be a very weak inducer of AmpC expression, consistent with the low PBP4 affinity documented.

scholarly journals Enterobactin- and salmochelin-β-lactam conjugates induce cell morphologies consistent with inhibition of penicillin-binding proteins in uropathogenic Escherichia coli CFT073

2021 ◽  
Author(s):  
Artur Sargun ◽  
Timothy C. Johnstone ◽  
Hui Zhi ◽  
Manuela Raffatellu ◽  
Elizabeth M. Nolan
Keyword(s):  
Escherichia Coli ◽  
Binding Proteins ◽  
Uropathogenic Escherichia Coli ◽  
Penicillin Binding Proteins ◽  
E Coli

Siderophore-β-lactam conjugates based on enterobactin and diglucosylated enterobactin enter the periplasm of uropathogenic E. coli CFT073 via the FepA and IroN transporters, and target penicillin-binding proteins.

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