|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 by microdilution method
|
Pseudomonas aeruginosa
|
1.22
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Concentration-effect relationship of ceftazidime explains why the time above the MIC is 40 percent for a static effect in vivo.
Year : 2007
Volume : 51
Issue : 9
First Page : 3449
Last Page : 3451
Authors : Mouton JW, Punt N, Vinks AA.
Abstract : Growth-kill dynamics were characterized in vitro, and the parameter estimates were used to simulate bacterial growth and kill in vivo using both mouse and human pharmacokinetics. The parameter estimates obtained in vitro predicted a time above the MIC of between 35 and 38% for a static effect in mice after 24 h of treatment.
|
Inhibition of bocillin FL binding to Pseudomonas aeruginosa PAO1 penicillin-binding protein 1b
|
Pseudomonas aeruginosa PAO1
|
5.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Pseudomonas aeruginosa PAO1 penicillin-binding protein 1a
|
Pseudomonas aeruginosa PAO1
|
0.2
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 6
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 5
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 4
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 3
|
Escherichia coli
|
0.07
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 2
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 1b
|
Escherichia coli
|
1.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Escherichia coli MC4100 penicillin-binding protein 1a
|
Escherichia coli
|
1.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Pseudomonas aeruginosa PAO1 penicillin-binding protein 2
|
Pseudomonas aeruginosa PAO1
|
32.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Pseudomonas aeruginosa PAO1 penicillin-binding protein 3
|
Pseudomonas aeruginosa PAO1
|
0.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Pseudomonas aeruginosa PAO1 penicillin-binding protein 4
|
Pseudomonas aeruginosa PAO1
|
2.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to Pseudomonas aeruginosa PAO1 penicillin-binding protein 5/6
|
Pseudomonas aeruginosa PAO1
|
32.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of bocillin FL binding to methicillin-resistant Staphylococcus aureus OC 3726 penicillin-binding protein 2a
|
Staphylococcus aureus
|
50.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.
Year : 2007
Volume : 51
Issue : 7
First Page : 2621
Last Page : 2624
Authors : Davies TA, Page MG, Shang W, Andrew T, Kania M, Bush K.
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.
|
Inhibition of PBP1 in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
0.9
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of PBP2 in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
0.5
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of PBP3 in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
0.04
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of PBP4 in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
200.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of PBP5 in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
200.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of low-affinity PBP5fm in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
200.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of PBP6 in penicillin-resistant Enterococcus faecium D63r membranes assessed as inhibition of fluorescent ampicillin binding after 20 mins at 37 degC
|
Enterococcus faecium
|
50.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Interaction of ceftobiprole with the low-affinity PBP 5 of Enterococcus faecium.
Year : 2010
Volume : 54
Issue : 2
First Page : 953
Last Page : 955
Authors : Henry X, Amoroso A, Coyette J, Joris B.
Abstract : Ceftobiprole is a new cephalosporin that exhibits a high level of affinity for methicillin-resistant Staphylococcus aureus PBP 2a. It was reported that ceftobiprole did not interact with a mutated form of the low-affinity protein Enterococcus faecium PBP 5 (PBP 5fm) that, when overexpressed, confers a beta-lactam resistance phenotype to the bacterium. Our results show that ceftobiprole binds to unmutated PBP 5fm to form a stable acyl-enzyme and that ceftobiprole is able to efficiently kill a penicillin-resistant Enterococcus faecium strain that produces this protein.
|
Inhibition of Bocillin FL binding to PBP1A in Escherichia coli MC4100 membranes
|
Escherichia coli
|
1.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP1B in Escherichia coli MC4100 membranes
|
Escherichia coli
|
1.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP2 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP3 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
0.07
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP4 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP5 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP6 in Escherichia coli MC4100 membranes
|
Escherichia coli
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP1A in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.2
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP1B in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
3.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP2 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
32.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP3 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
0.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP4 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
2.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP5/6 in Pseudomonas aeruginosa PAO1 membranes
|
Pseudomonas aeruginosa PAO1
|
32.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP1A in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.3
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP1B in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
1.6
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP2 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP3 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
0.1
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP4 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
2.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Inhibition of Bocillin FL binding to PBP5/6 in Pseudomonas aeruginosa 27853 membranes
|
Pseudomonas aeruginosa PAO1
|
4.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa.
Year : 2008
Volume : 52
Issue : 4
First Page : 1510
Last Page : 1512
Authors : Davies TA, Shang W, Bush K, Flamm RK.
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.
|
Antibacterial activity against Escherichia coli TP1 harboring pBR322 carrying TEM-1 assessed as inhibition of bacterial growth at 2 ug/ml after 18 hrs
|
Escherichia coli
|
99.0
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Fitness trade-offs in blaTEM evolution.
Year : 2008
Volume : 52
Issue : 7
First Page : 2340
Last Page : 2345
Authors : Mroczkowska JE, Barlow M.
Abstract : bla(TEM-1) expression results in penicillin resistance, whereas expression of many bla(TEM-1) descendants, called extended-spectrum beta-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla(TEM-1) is still the most abundant bla(TEM) allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla(TEM-1) descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla(TEM-1), bla(TEM-10), and bla(TEM-12). Our results show that bacteria expressing the ancestral bla(TEM-1) allele have a fitness advantage over those expressing either bla(TEM-10) or bla(TEM-12) when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla(TEM-1) has persisted as the most frequently encountered bla(TEM) allele in bacterial populations.
|
Antibacterial activity against Escherichia coli TP1 harboring pBR322 carrying TEM-10 assessed as bacterial density up to 64 ug/ml after 18 hrs
|
Escherichia coli
|
100.0
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Fitness trade-offs in blaTEM evolution.
Year : 2008
Volume : 52
Issue : 7
First Page : 2340
Last Page : 2345
Authors : Mroczkowska JE, Barlow M.
Abstract : bla(TEM-1) expression results in penicillin resistance, whereas expression of many bla(TEM-1) descendants, called extended-spectrum beta-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla(TEM-1) is still the most abundant bla(TEM) allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla(TEM-1) descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla(TEM-1), bla(TEM-10), and bla(TEM-12). Our results show that bacteria expressing the ancestral bla(TEM-1) allele have a fitness advantage over those expressing either bla(TEM-10) or bla(TEM-12) when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla(TEM-1) has persisted as the most frequently encountered bla(TEM) allele in bacterial populations.
|
Antibacterial activity against Escherichia coli TP1 harboring pBR322 carrying TEM-10 assessed as inhibition of bacterial growth at 256 ug/ml after 18 hrs
|
Escherichia coli
|
17.0
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Fitness trade-offs in blaTEM evolution.
Year : 2008
Volume : 52
Issue : 7
First Page : 2340
Last Page : 2345
Authors : Mroczkowska JE, Barlow M.
Abstract : bla(TEM-1) expression results in penicillin resistance, whereas expression of many bla(TEM-1) descendants, called extended-spectrum beta-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla(TEM-1) is still the most abundant bla(TEM) allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla(TEM-1) descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla(TEM-1), bla(TEM-10), and bla(TEM-12). Our results show that bacteria expressing the ancestral bla(TEM-1) allele have a fitness advantage over those expressing either bla(TEM-10) or bla(TEM-12) when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla(TEM-1) has persisted as the most frequently encountered bla(TEM) allele in bacterial populations.
|
Antibacterial activity against Escherichia coli TP1 harboring pBR322 carrying TEM-12 assessed as inhibition of bacterial growth at 64 ug/ml after 18 hrs
|
Escherichia coli
|
64.0
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Fitness trade-offs in blaTEM evolution.
Year : 2008
Volume : 52
Issue : 7
First Page : 2340
Last Page : 2345
Authors : Mroczkowska JE, Barlow M.
Abstract : bla(TEM-1) expression results in penicillin resistance, whereas expression of many bla(TEM-1) descendants, called extended-spectrum beta-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla(TEM-1) is still the most abundant bla(TEM) allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla(TEM-1) descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla(TEM-1), bla(TEM-10), and bla(TEM-12). Our results show that bacteria expressing the ancestral bla(TEM-1) allele have a fitness advantage over those expressing either bla(TEM-10) or bla(TEM-12) when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla(TEM-1) has persisted as the most frequently encountered bla(TEM) allele in bacterial populations.
|
Antibacterial activity against Escherichia coli TP1 harboring pBR322 carrying TEM-12 assessed as inhibition of bacterial growth at 256 ug/ml after 18 hrs
|
Escherichia coli
|
88.0
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Fitness trade-offs in blaTEM evolution.
Year : 2008
Volume : 52
Issue : 7
First Page : 2340
Last Page : 2345
Authors : Mroczkowska JE, Barlow M.
Abstract : bla(TEM-1) expression results in penicillin resistance, whereas expression of many bla(TEM-1) descendants, called extended-spectrum beta-lactamases (ESBLs), results simultaneously in resistance to penicillins and extended-spectrum cephalosporins. Despite the expanded resistance phenotypes conferred by many ESBLs, bla(TEM-1) is still the most abundant bla(TEM) allele in many microbial populations. This study examines the fitness effects of the two amino acid substitutions, R164S and E240K, that have occurred repeatedly among ESBL bla(TEM-1) descendants. Using a single-nucleotide polymorphism-specific real-time quantitative PCR method, we analyzed the fitness of strains expressing bla(TEM-1), bla(TEM-10), and bla(TEM-12). Our results show that bacteria expressing the ancestral bla(TEM-1) allele have a fitness advantage over those expressing either bla(TEM-10) or bla(TEM-12) when exposed to ampicillin. This observation, combined with the fact that penicillins are the most prevalent antimicrobials prescribed worldwide, may explain why bla(TEM-1) has persisted as the most frequently encountered bla(TEM) allele in bacterial populations.
|
Inhibition of Escherichia coli MC4100 Beta-Lactamase CMY-30 using cephalothin as reporter substrate
|
Escherichia coli
|
140.0
nM
|
|
Journal : Antimicrob. Agents Chemother.
Title : Extended-spectrum properties of CMY-30, a Val211Gly mutant of CMY-2 cephalosporinase.
Year : 2009
Volume : 53
Issue : 8
First Page : 3520
Last Page : 3523
Authors : Kotsakis SD, Papagiannitsis CC, Tzelepi E, Tzouvelekis LS, Miriagou V.
Abstract : CMY-30, a Val211Gly mutant of CMY-2 cephalosporinase, was derived by mutagenesis. The hydrolytic efficiency of CMY-30 against expanded-spectrum cephalosporins was higher than that of CMY-2 due to increased k(cat) values. Findings indicate a role of the Omega loop residue 211 in determining the substrate specificities of CMYs also corroborated by modeling studies.
|
Inhibition of Escherichia coli MC4100 Beta-Lactamase CMY-2 using cephalothin as reporter substrate
|
Escherichia coli
|
20.0
nM
|
|
Journal : Antimicrob. Agents Chemother.
Title : Extended-spectrum properties of CMY-30, a Val211Gly mutant of CMY-2 cephalosporinase.
Year : 2009
Volume : 53
Issue : 8
First Page : 3520
Last Page : 3523
Authors : Kotsakis SD, Papagiannitsis CC, Tzelepi E, Tzouvelekis LS, Miriagou V.
Abstract : CMY-30, a Val211Gly mutant of CMY-2 cephalosporinase, was derived by mutagenesis. The hydrolytic efficiency of CMY-30 against expanded-spectrum cephalosporins was higher than that of CMY-2 due to increased k(cat) values. Findings indicate a role of the Omega loop residue 211 in determining the substrate specificities of CMYs also corroborated by modeling studies.
|
Inhibition of Pseudomonas aeruginosa PAO1 PBP1b by SDS-PAGE
|
Pseudomonas aeruginosa PAO1
|
0.12
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa.
Year : 2010
Volume : 54
Issue : 9
First Page : 3933
Last Page : 3937
Authors : Moyá B, Zamorano L, Juan C, Ge Y, Oliver A.
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 microg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1x the MIC (0.5 microg/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 0.5x 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 > or = 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.
|
Inhibition of Pseudomonas aeruginosa PAO1 PBP1c by SDS-PAGE
|
Pseudomonas aeruginosa PAO1
|
2.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa.
Year : 2010
Volume : 54
Issue : 9
First Page : 3933
Last Page : 3937
Authors : Moyá B, Zamorano L, Juan C, Ge Y, Oliver A.
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 microg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1x the MIC (0.5 microg/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 0.5x 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 > or = 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.
|
Inhibition of Pseudomonas aeruginosa PAO1 PBP2 by SDS-PAGE
|
Pseudomonas aeruginosa PAO1
|
2.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa.
Year : 2010
Volume : 54
Issue : 9
First Page : 3933
Last Page : 3937
Authors : Moyá B, Zamorano L, Juan C, Ge Y, Oliver A.
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 microg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1x the MIC (0.5 microg/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 0.5x 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 > or = 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.
|
Inhibition of Pseudomonas aeruginosa PAO1 PBP3 by SDS-PAGE
|
Pseudomonas aeruginosa PAO1
|
0.04
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa.
Year : 2010
Volume : 54
Issue : 9
First Page : 3933
Last Page : 3937
Authors : Moyá B, Zamorano L, Juan C, Ge Y, Oliver A.
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 microg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1x the MIC (0.5 microg/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 0.5x 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 > or = 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.
|
Inhibition of Pseudomonas aeruginosa PAO1 PBP4 by SDS-PAGE
|
Pseudomonas aeruginosa PAO1
|
1.23
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa.
Year : 2010
Volume : 54
Issue : 9
First Page : 3933
Last Page : 3937
Authors : Moyá B, Zamorano L, Juan C, Ge Y, Oliver A.
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 microg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1x the MIC (0.5 microg/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 0.5x 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 > or = 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.
|
Inhibition of Pseudomonas aeruginosa PAO1 PBP5/6 by SDS-PAGE
|
Pseudomonas aeruginosa PAO1
|
2.0
ug.mL-1
|
|
Journal : Antimicrob. Agents Chemother.
Title : Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa.
Year : 2010
Volume : 54
Issue : 9
First Page : 3933
Last Page : 3937
Authors : Moyá B, Zamorano L, Juan C, Ge Y, Oliver A.
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 microg/ml, respectively. Killing curves revealed that CXA-101 shows a concentration-independent bactericidal activity, with concentrations of 1x the MIC (0.5 microg/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 0.5x 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 > or = 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.
|
Inhibition of wild type His-tagged translin/trax E126A mutant (unknown origin) coexpressed in Escherichia coli BL21 cells using RNase Alert as substrate at 30 uM incubated for 10 mins prior to substrate addition monitored over 60 mins by fluorescence assay
|
Homo sapiens
|
100.0
%
|
|
Journal : Bioorg Med Chem Lett
Title : A druggable target for rescuing microRNA defects.
Year : 2016
Volume : 26
Issue : 20
First Page : 4942
Last Page : 4946
Authors : Asada K, Canestrari E, Paroo Z.
Abstract : Despite immense promise, development of microRNA (miRNA) therapeutics remains limited by pharmacodynamic challenges that have hindered progress of related oligonucleotide-based technologies. Recent discovery of enzymes that mediate miRNA metabolism represent potential pharmacological targets for directing miRNA function, circumventing barriers associated with oligonucleotides. We previously identified the Translin/Trax (TN/TX) ribonuclease complex as a pre-miRNA degrading enzyme that competes with pre-miRNA processing by Dicer. Here, we establish a high-throughput TN/TX assay and screened 2320 drug and natural product compounds for inhibitors of TN/TX. Secondary analyses demonstrate small molecule mediated inhibition of pre-miRNA degradation by TN/TX and enhanced miRNA processing by Dicer. This application of traditional enzyme-inhibitor pharmacology to the miRNA pathway establishes a druggable target for rescuing global miRNA defects, providing an important complement to current approaches towards miRNA therapeutics. More broadly, demonstrating feasibility of pharmacological targeting of the 'ribonucleome' is particularly important given emerging classes of regulatory RNA and growing understanding of their importance in health and disease.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
-10.11
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
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SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
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Severe acute respiratory syndrome coronavirus 2
|
12.78
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
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Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
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Chlorocebus sabaeus
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-0.15
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.15
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
