Journal:

Article Title: Bactericidal Activity of Vancomycin in Cerebrospinal Fluid

doi:

Figure Lengend Snippet: In vitro activities of the indicated concentrations of vancomycin against S. aureus ATCC 25923 (A) and S. epidermidis ATCC 12228 (B) within human CSF samples at 37°C. Mean ± standard errors of the means of 10 (2, 5, 100, and 300 μg/ml) or 20 (0 and 10 μg/ml) samples each are depicted. Also shown in panel B is the mean activity for vancomycin concentrations of 10, 100, and 300 μg/ml in the infant’s CSF enriched with his clinical isolate of S. epidermidis.

Article Snippet: A concentration of 5 μg/ml showed a slightly lower activity than concentrations of 10 to 300 μg/ml after 48 h, but this difference was not significant. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window FIG. 1 caption a7 In vitro activities of the indicated concentrations of vancomycin against S. aureus ATCC 25923 (A) and S. epidermidis ATCC 12228 (B) within human CSF samples at 37°C.

Techniques: In Vitro, Activity Assay

Journal: Journal of Medicinal Chemistry

Article Title: Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities

doi: 10.1021/acs.jmedchem.4c00912

Figure Lengend Snippet: Computational design of TBP-forming peptides. Mutations favoring TBP stabilization in the “scaled” Martini simulations. (a) Helical wheel diagram of LP1, simulation snapshots of hexameric LP1 TBP, and the effect of “N-shift” motions (black arrows) on the stability of intermolecular salt bridges and aromatic stacking interactions in LP1 TBP. LP1 interaction strengths are used as a reference (orange lines). (b) Stronger aromatic stacking on the second peptide–peptide interface of hexameric LP6 TBP using I26F substitution. (c) Stronger salt bridges resulted in octameric LP14 and heptameric LP15 TBPs. (d) Shorter N-terminal K-cluster decreased the N-shift and stabilized heptameric LP17 TBP. (e) Carboxy-terminus and complementary stacking with I26F resulted in an octameric LP26 TBP. (f) T/S substitutions caused tight packing of polar faces, resulting in narrower but octameric LP34 and LP36 TBPs. Neutral H-containing peptide ends (H ends) and carboxy-terminus resulted in octameric LP40 TBP. Snapshots were taken after 51 μs simulation using the “scaled” Martini force field, showing the side and top views of TBPs in the POPC lipid membrane. Schematic illustrations are shown for three antiparallel neighboring transmembrane peptides representing two peptide–peptide interfaces of a TBP (side and top views). Stability of stacking and salt bridge interactions was calculated as the percentage of designed interaction contacts averaged over 51 μs simulation using the standard and “scaled” Martini force fields ( Table ). Color coding: peptide hydrophilic and hydrophobic residues in green and white, respectively; basic and acidic in residues blue and red, respectively; aromatic residues in gray; membrane lipid phosphates in yellow and tails as gray panel; and yellow horizontal lines in the schematic illustrations indicate the position of lipid phosphates.

Article Snippet: Second, LP28, with an MIC of 800 nM, was more active than LP1 against E. faecium (ATCC 700221; resistant to vancomycin), P. aeruginosa (PAO1 and PA14), and E. coli (ATCC 11775) and equally active against A. baumannii (ATCC 19606) and E. coli (AIC221).

Techniques: Membrane

Journal: Journal of Medicinal Chemistry

Article Title: Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities

doi: 10.1021/acs.jmedchem.4c00912

Figure Lengend Snippet: Computational design of peptides with switched charge distribution stabilizing TBPs. Mutations favoring TBP stabilization in the “scaled” Martini simulation. Helical wheel diagram (a), simulation snapshots of TBPs (a, b), schematic illustrations of “C-shift” motions (black arrows) and the intermolecular interactions, and the strength of these interactions in TBPs (a–c; orange lines indicate LP1 reference). Snapshots were captured after 51 μs simulation using “scaled” Martini force field, showing the side and top views of TBPs in POPC lipid membrane. Schematic illustrations represent three antiparallel neighboring transmembrane peptides with two peptide–peptide interfaces from a TBP (side and top views). Stability of aromatic stacking and salt bridge interactions was calculated as the percentage of designed interaction contacts averaged over 51 μs simulation using the standard and “scaled” Martini force fields ( Table ). Color coding: peptide hydrophilic and hydrophobic residues in green and white, respectively; basic and acidic residues in blue and red, respectively; aromatic residues in gray; membrane lipid phosphates in yellow and tails as gray panel; and yellow horizontal lines in the schematic illustrations indicate the position of lipid phosphates.

Article Snippet: Second, LP28, with an MIC of 800 nM, was more active than LP1 against E. faecium (ATCC 700221; resistant to vancomycin), P. aeruginosa (PAO1 and PA14), and E. coli (ATCC 11775) and equally active against A. baumannii (ATCC 19606) and E. coli (AIC221).

Techniques: Membrane

Journal: Journal of Medicinal Chemistry

Article Title: Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities

doi: 10.1021/acs.jmedchem.4c00912

Figure Lengend Snippet: Anti-infective activity in the deep thigh infection mouse model. (a) Schematic of the deep thigh infection model in which bacteria are injected intramuscularly at day 4 and peptides are administered intraperitoneally also at day 4 to assess their anti-infective activity. Mice were euthanized 4 days postinfection (day 8). Each group consisted of six mice ( n = 6), and the bacterial loads used to infect the mice derived from three different inocula. (b) Intraperitoneal treatment with the peptides at 10-fold MIC (i.e., LP1: 0.16 mg/kg, LP18: 0.17 mg/kg, LP28: 0.18 mg/kg, LP40: 1.33 mg/kg) reduced the bacterial load of A. baumannii (ATCC 19606) compared to the untreated control group. Polymyxin B (0.006 mg/kg) and levofloxacin (0.014 mg/kg) were used as the reference antibiotics. Statistical significance was done using one-way ANOVA followed by Dunnett’s test. Violin plots represent the median, upper quartile, and lower quartile. (c) Mouse weight was monitored to exclude possible toxic effects of the peptides. Peptide sequences are shown in Table .

Article Snippet: Second, LP28, with an MIC of 800 nM, was more active than LP1 against E. faecium (ATCC 700221; resistant to vancomycin), P. aeruginosa (PAO1 and PA14), and E. coli (ATCC 11775) and equally active against A. baumannii (ATCC 19606) and E. coli (AIC221).

Techniques: Activity Assay, Infection, Bacteria, Injection, Derivative Assay, Control

Journal: Journal of Medical Microbiology

Article Title: Current concepts on the virulence mechanisms of meticillin-resistant Staphylococcus aureus

doi: 10.1099/jmm.0.043513-0

Figure Lengend Snippet: Studies demonstrating the pathogenic mechanisms and potential of Panton–Valentine leukocidin

Article Snippet: Indeed, further evidence of the poor activity of vancomycin against MRSA biofilm (using strain ATCC 43300) was demonstrated in experiments that combined vancomycin with rifampicin ( Salem et al. , 2010 ).

Techniques: In Vitro, Purification, Knock-Out, Gene Expression, Competitive Binding Assay, Concentration Assay, Infection, Variant Assay, Lysis, Bacteria, Binding Assay, Microarray, Derivative Assay

Journal: Journal of Medical Microbiology

Article Title: Current concepts on the virulence mechanisms of meticillin-resistant Staphylococcus aureus

doi: 10.1099/jmm.0.043513-0

Figure Lengend Snippet: Steps in MRSA biofilm formation. Reproduced with permission from J. M. Ghigo, Institut Pasteur, Paris, France.

Article Snippet: Indeed, further evidence of the poor activity of vancomycin against MRSA biofilm (using strain ATCC 43300) was demonstrated in experiments that combined vancomycin with rifampicin ( Salem et al. , 2010 ).

Techniques: