Journal: European Journal of Medicinal Chemistry

Article Title: Structure-activity relationships of potentiators of the antibiotic activity of clarithromycin against Escherichia coli

doi: 10.1016/j.ejmech.2019.05.075

Figure Lengend Snippet: Figure 3. Membrane permeabilization assays of 16 in E. coli ATCC 25922. Polymyxin B was included as a comparator membrane-targeting agent. Both 16 and polymyxin B were used at concentrations ranging from 1/32X to 1/2X the minimum inhibitory concentration (MIC), with the MIC values of 16 and polymyxin B being 100 and 1.56 µg/ml, respectively. The compound vehicle was DMSO. (A,B) Impact of E. coli treatment with 16 (A) or polymyxin B (B) on the intensity of the fluorophore N- phenyl-1-naphthylamine (NPN) at a concentration of 10 µM. (C,D) Impact of treatment with 16 (C) or polymyxin B (D) on the percentage of E. coli cells stained with the fluorophore propidium iodide (PI) at a concentration of 50 µM.

Article Snippet: M AN US CR IP T AC CE PT ED Graphical Abstract Compound 16 is associated with a 32-fold enhancement in the potency of clarithromycin against E. coli ATCC 25922 in vitro Graphical Abstract Compound 16 is associated with a 32-fold enhancement in the potency of clarithromycin against E. coli ATCC 25922 in vitro H2N H N NH2 16 H2N H N NH2 16 M AN US CR IP T AC CE PT ED -1- Structure-Activity Relationships of Potentiators of the Antibiotic Activity of Clarithromycin against Escherichia coli Gifty Blanksona, Ajit K. Parhia,c, Malvika Kaulb, Daniel S. Pilchb and Edmond J. LaVoiea aDepartment of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08820, U.S.A. bDepartment of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, U.S.A cTAXIS Pharmaceuticals, Inc., Monmouth Junction, New Jersey 08552, U.S.A. 1.

Techniques: Membrane, Concentration Assay, Staining

Journal: European Journal of Medicinal Chemistry

Article Title: Structure-activity relationships of potentiators of the antibiotic activity of clarithromycin against Escherichia coli

doi: 10.1016/j.ejmech.2019.05.075

Figure Lengend Snippet: Figure 4. Assay for inhibition of the efflux of the fluorophore Hoechst 33342 (H33342) by 16 in E. coli ATCC 25922. When present, 16 was used at concentrations ranging from 1/32X to 1/2X MIC (3.13 to 50 µg/mL). All reactions were initiated by the addition of 50 mM glucose except where indicated. H33342 was used at a concentration of 10 µM. Compound vehicle was DMSO.

Article Snippet: M AN US CR IP T AC CE PT ED Graphical Abstract Compound 16 is associated with a 32-fold enhancement in the potency of clarithromycin against E. coli ATCC 25922 in vitro Graphical Abstract Compound 16 is associated with a 32-fold enhancement in the potency of clarithromycin against E. coli ATCC 25922 in vitro H2N H N NH2 16 H2N H N NH2 16 M AN US CR IP T AC CE PT ED -1- Structure-Activity Relationships of Potentiators of the Antibiotic Activity of Clarithromycin against Escherichia coli Gifty Blanksona, Ajit K. Parhia,c, Malvika Kaulb, Daniel S. Pilchb and Edmond J. LaVoiea aDepartment of Medicinal Chemistry, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08820, U.S.A. bDepartment of Pharmacology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, U.S.A cTAXIS Pharmaceuticals, Inc., Monmouth Junction, New Jersey 08552, U.S.A. 1.

Techniques: Inhibition, Concentration Assay

Journal:

Article Title: Characteristics and Dynamics of Bacterial Populations during Postantibiotic Effect Determined by Flow Cytometry

doi:

Figure Lengend Snippet: MICs, multiples of MICs, and duration of PAEs for organism-antibiotic combinations studied by flow cytometry

Article Snippet: Growth curves from typical PAE experiments with ceftriaxone and ciprofloxacin (each at a concentration equivalent to twice the MIC) against E. coli are shown in Fig. A. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism Antibiotic MIC (μg/ml) Multiple of MIC PAE (h) E. coli ATCC 25922 Ampicillin 2.0 2 −0.3 4 −0.4 8 −0.3 Ceftriaxone 0.03 2 −0.3 4 −0.2 8 −0.5 Gentamicin 1.0 1 0.7 2 0.6 Ciprofloxacin 0.015 1 1.5 2 2.7 Rifampin 16 1 0.6 2 1.5 P. aeruginosa ATCC 27853 Imipenem 2.0 2 1.3 4 1.9 8 2.6 Ciprofloxacin 0.5 2 0.7 Open in a separate window MICs, multiples of MICs, and duration of PAEs for organism-antibiotic combinations studied by flow cytometry fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1 caption a7 (A) A typical PAE experiment for E. coli ATCC 25922 after exposure to ceftriaxone or ciprofloxacin (each at a concentration equivalent to twice the MIC), as determined by viability counting.

Techniques:

Journal:

Article Title: Characteristics and Dynamics of Bacterial Populations during Postantibiotic Effect Determined by Flow Cytometry

doi:

Figure Lengend Snippet: (A) A typical PAE experiment for E. coli ATCC 25922 after exposure to ceftriaxone or ciprofloxacin (each at a concentration equivalent to twice the MIC), as determined by viability counting. As shown, no PAE was seen after ceftriaxone exposure, but ciprofloxacin induced a PAE of 1.9 h. The organisms were stained with propidium iodide and examined by fluorescence microscopy. (B through D) Photomicrographs of untreated control organisms (B), ceftriaxone-exposed organisms 35 min after drug removal (C), and ciprofloxacin-exposed organisms 270 min after drug removal (D). Both antibiotics induced filamentation, but this morphological form persisted past the classically defined PAE in organisms exposed to ciprofloxacin. Magnification, ×880.

Article Snippet: Growth curves from typical PAE experiments with ceftriaxone and ciprofloxacin (each at a concentration equivalent to twice the MIC) against E. coli are shown in Fig. A. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism Antibiotic MIC (μg/ml) Multiple of MIC PAE (h) E. coli ATCC 25922 Ampicillin 2.0 2 −0.3 4 −0.4 8 −0.3 Ceftriaxone 0.03 2 −0.3 4 −0.2 8 −0.5 Gentamicin 1.0 1 0.7 2 0.6 Ciprofloxacin 0.015 1 1.5 2 2.7 Rifampin 16 1 0.6 2 1.5 P. aeruginosa ATCC 27853 Imipenem 2.0 2 1.3 4 1.9 8 2.6 Ciprofloxacin 0.5 2 0.7 Open in a separate window MICs, multiples of MICs, and duration of PAEs for organism-antibiotic combinations studied by flow cytometry fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1 caption a7 (A) A typical PAE experiment for E. coli ATCC 25922 after exposure to ceftriaxone or ciprofloxacin (each at a concentration equivalent to twice the MIC), as determined by viability counting.

Techniques: Concentration Assay, Staining, Fluorescence, Microscopy

Journal:

Article Title: Characteristics and Dynamics of Bacterial Populations during Postantibiotic Effect Determined by Flow Cytometry

doi:

Figure Lengend Snippet: Histograms showing a comparison of the size distributions (FSC-H; left panels) and nucleic acid contents (FL2-H; middle panels) of E. coli during the PAE after exposure to ciprofloxacin at a concentration equivalent to the MIC and at a concentration equivalent to twice the MIC at 270 min after drug removal. Dotted-and-dashed lines, control organisms; solid lines, bacteria previously exposed to ciprofloxacin. Graphs (right panels) show progressive changes in size compared to sizes of controls. The sizes of antibiotic-treated organisms were compared to three control size intervals described in the text and shown in Fig. ​Fig.2.2. Open circles, bacteria within 2 SDs of control size; solid squares, bacteria within 2 to 4 SDs; open squares, organisms >4 SDs from the control distribution.

Article Snippet: Growth curves from typical PAE experiments with ceftriaxone and ciprofloxacin (each at a concentration equivalent to twice the MIC) against E. coli are shown in Fig. A. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism Antibiotic MIC (μg/ml) Multiple of MIC PAE (h) E. coli ATCC 25922 Ampicillin 2.0 2 −0.3 4 −0.4 8 −0.3 Ceftriaxone 0.03 2 −0.3 4 −0.2 8 −0.5 Gentamicin 1.0 1 0.7 2 0.6 Ciprofloxacin 0.015 1 1.5 2 2.7 Rifampin 16 1 0.6 2 1.5 P. aeruginosa ATCC 27853 Imipenem 2.0 2 1.3 4 1.9 8 2.6 Ciprofloxacin 0.5 2 0.7 Open in a separate window MICs, multiples of MICs, and duration of PAEs for organism-antibiotic combinations studied by flow cytometry fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1 caption a7 (A) A typical PAE experiment for E. coli ATCC 25922 after exposure to ceftriaxone or ciprofloxacin (each at a concentration equivalent to twice the MIC), as determined by viability counting.

Techniques: Concentration Assay

Journal:

Article Title: Characteristics and Dynamics of Bacterial Populations during Postantibiotic Effect Determined by Flow Cytometry

doi:

Figure Lengend Snippet: Histograms showing the size distributions (FSC-H; left panels) and nucleic acid contents (FL2-H; middle panels) of P. aeruginosa during the PAE after exposure to imipenem at a concentration equivalent to twice the MIC and to ciprofloxacin at a concentration equivalent to the MIC at 180 and 70 min after drug removal, respectively. Dotted-and-dashed lines, control organisms; solid lines, antibiotic-exposed organisms. The graphs (right panels) show progressive changes in size compared to sizes of controls. The sizes of antibiotic-treated organisms were compared to three control size intervals described in text and shown in Fig. ​Fig.2.2. Open circles, bacteria within 2 SDs of control size; solid squares, bacteria within 2 to 4 SDs; open squares, organisms >4 SDs from the control distribution.

Article Snippet: Growth curves from typical PAE experiments with ceftriaxone and ciprofloxacin (each at a concentration equivalent to twice the MIC) against E. coli are shown in Fig. A. table ft1 table-wrap mode="anchored" t5 TABLE 1 caption a7 Organism Antibiotic MIC (μg/ml) Multiple of MIC PAE (h) E. coli ATCC 25922 Ampicillin 2.0 2 −0.3 4 −0.4 8 −0.3 Ceftriaxone 0.03 2 −0.3 4 −0.2 8 −0.5 Gentamicin 1.0 1 0.7 2 0.6 Ciprofloxacin 0.015 1 1.5 2 2.7 Rifampin 16 1 0.6 2 1.5 P. aeruginosa ATCC 27853 Imipenem 2.0 2 1.3 4 1.9 8 2.6 Ciprofloxacin 0.5 2 0.7 Open in a separate window MICs, multiples of MICs, and duration of PAEs for organism-antibiotic combinations studied by flow cytometry fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1 caption a7 (A) A typical PAE experiment for E. coli ATCC 25922 after exposure to ceftriaxone or ciprofloxacin (each at a concentration equivalent to twice the MIC), as determined by viability counting.

Techniques: Concentration Assay