Journal: PLoS Pathogens

Article Title: Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

doi: 10.1371/journal.ppat.1007084

Figure Lengend Snippet: In vitro MICs of antibiotics and peptides against clinical isolates.

Article Snippet: Bacterial strains used in this study were E . faecium #1–1 (BEI resources, NR-31903), K . pneumonia KPLN649 [ ], A . baumannii Ab5075 [ ], P . aeruginosa LESB58 [ ], E . cloacae 218R1 [ ], E . coli E38 (Serotype O78:H-) (BEI resources, NR-17717), and S . aureus LAC USA300 [ ] ( ).

Techniques: In Vitro

Journal: PLoS Pathogens

Article Title: Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

doi: 10.1371/journal.ppat.1007084

Figure Lengend Snippet: CD-1 female mice were injected with individual bacterial strains carrying plasmids constitutively expressing lux reporter genes. Bacterial strains were injected subcutaneously at a dose of 1 × 10 9 CFU E . faecium , 5 × 10 7 CFU S . aureus , 1 × 10 9 CFU K . pneumoniae , 1 × 10 9 CFU A . baumannii , 5 × 10 7 CFU P . aeruginosa , 2.5 × 10 8 CFU E . cloacae , and 1 × 10 8 CFU E . coli . The infection was monitored 1 h post infection and then every 24 h until day 3. Representative images for day 0 and day 3 are shown. Mice were imaged using a Perkin Elmer in vivo imaging system (IVIS) and the experiment was repeated twice with three mice/group. The scale at the bottom indicates radiance x 10 6 .

Article Snippet: Bacterial strains used in this study were E . faecium #1–1 (BEI resources, NR-31903), K . pneumonia KPLN649 [ ], A . baumannii Ab5075 [ ], P . aeruginosa LESB58 [ ], E . cloacae 218R1 [ ], E . coli E38 (Serotype O78:H-) (BEI resources, NR-17717), and S . aureus LAC USA300 [ ] ( ).

Techniques: Injection, Expressing, Infection, In Vivo Imaging

Journal: PLoS Pathogens

Article Title: Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

doi: 10.1371/journal.ppat.1007084

Figure Lengend Snippet: Bacterial strains were injected subcutaneously and treated one hour post infection with either saline (control), synthetic peptides, antibiotics, or antibiotic-peptide combinations. Synthetic peptide concentrations for all conditions were as follows: 1002, 10 mg/kg (3 mg/kg for E . faecium ); 1018, 10 mg/kg; HHC-10 10 mg/kg, and DJK-5, 3 mg/kg (0.25 mg/kg for S . aureus ). Infected and inflamed tissue was measured three days post infection and pus-containing abscess lumps excised to determine CFU. Abscess sizes are in box and whiskers plots (left panel) and counted CFU/abscess data expressed with geometric mean (right panel). A . P . aeruginosa LESB58, ciprofloxacin 0.4 mg/kg. B . A . baumannii Ab5075, erythromycin 6 mg/kg, meropenem 6 mg/kg. C . K . pneumoniae KPLN649, meropenem 10 mg/kg, ciprofloxacin 30 mg/kg. D . E . cloacae 218 R1, ciprofloxacin 0.006 mg/kg. E . E . coli E38, ciprofloxacin 4 mg/kg, F. E . faecium #1–1, gentamicin 16 mg/kg. G. S . aureus LAC, clindamycin 0.01 mg/kg; vancomycin 0.15 mg/kg. (A-G) n = 368 biologically independent animals. All experiments were done at least three times with 2–4 mice/group. Statistical analysis was performed using One-way ANOVA, Kruskal-Wallis test with Dunn’s correction (two-sided). The asterisk indicates significant differences to the wild-type (*, p < 0.05; **, p < 0.01; ***, p < 0.001). The hash indicates significant differences of the combination therapy over the sum of the effects of each agent alone (#, p < 0.05; ##, p < 0.01; ###, p < 0.001).

Article Snippet: Bacterial strains used in this study were E . faecium #1–1 (BEI resources, NR-31903), K . pneumonia KPLN649 [ ], A . baumannii Ab5075 [ ], P . aeruginosa LESB58 [ ], E . cloacae 218R1 [ ], E . coli E38 (Serotype O78:H-) (BEI resources, NR-17717), and S . aureus LAC USA300 [ ] ( ).

Techniques: Injection, Infection, Saline, Control

Journal: PLoS Pathogens

Article Title: Synergy between conventional antibiotics and anti-biofilm peptides in a murine, sub-cutaneous abscess model caused by recalcitrant ESKAPE pathogens

doi: 10.1371/journal.ppat.1007084

Figure Lengend Snippet: Outer membrane permeabilization by peptides cf. antibiotics at their corresponding MICs. The uptake of the fluorophore NPN in the presence of different antibiotics and synthetic peptides was determined by assessing increased fluorescence at an excitation wavelength of 350 nm and an emission wavelength of 420 nm due to partition of the normally impermeable hydrophobic NPN into bacterial membranes. Relative fluorescence values of at least three biological replicates were determined by subtracting the fluorescence value without test substance.

Article Snippet: Bacterial strains used in this study were E . faecium #1–1 (BEI resources, NR-31903), K . pneumonia KPLN649 [ ], A . baumannii Ab5075 [ ], P . aeruginosa LESB58 [ ], E . cloacae 218R1 [ ], E . coli E38 (Serotype O78:H-) (BEI resources, NR-17717), and S . aureus LAC USA300 [ ] ( ).

Techniques: Membrane, Fluorescence

Journal: Antimicrobial Agents and Chemotherapy

Article Title: In Vivo and In Vitro Effects of a ClpP-Activating Antibiotic against Vancomycin-Resistant Enterococci

doi: 10.1128/AAC.00424-18

Figure Lengend Snippet: Time-kill curves for stationary-phase E. faecalis V583 (VRE) with antibiotics alone (A) or in combination (B). Data for combinations with ADEP4 are shown with dotted lines. Antibiotics used were ampicillin (AMP), ciprofloxacin (CIP), daptomycin (DAP), gentamicin (GEN), linezolid (LZD), oritavancin (ORI), rifampin (RIF), and tigecycline (TGC). Error bars represent standard deviations. The x axis is at the limit of detection.

Article Snippet: E. faecalis strain V583 was used for the in vitro stationary-phase and biofilm killing experiments as well as the in vivo peritoneal septicemia model. Bacterial strains were obtained through the ATCC or BEI Resources or from academic labs (see Table S1 in the supplemental material).

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: In Vivo and In Vitro Effects of a ClpP-Activating Antibiotic against Vancomycin-Resistant Enterococci

doi: 10.1128/AAC.00424-18

Figure Lengend Snippet: Killing of mature E. faecalis V583 (VRE) biofilms by antibiotics alone or in combination with ADEP4 after 24, 48, or 72 h. Antibiotics used were ampicillin (AMP), ciprofloxacin (CIP), daptomycin (DAP), gentamicin (GEN), linezolid (LZD), oritavancin (ORI), rifampin (RIF), and tigecycline (TGC). Error bars represent standard deviations. The x axis is at the limit of detection.

Article Snippet: E. faecalis strain V583 was used for the in vitro stationary-phase and biofilm killing experiments as well as the in vivo peritoneal septicemia model. Bacterial strains were obtained through the ATCC or BEI Resources or from academic labs (see Table S1 in the supplemental material).

Techniques:

Journal: Antimicrobial Agents and Chemotherapy

Article Title: In Vivo and In Vitro Effects of a ClpP-Activating Antibiotic against Vancomycin-Resistant Enterococci

doi: 10.1128/AAC.00424-18

Figure Lengend Snippet: In vivo efficacies of ADEP4 alone and in combination with ampicillin (AMP) against murine peritonitis caused by E. faecalis V583 (VRE) infection. ADEP4 was dosed at 80 mg/kg. AMP was dosed at two concentrations: 50 mg/kg (50) and 100 mg/kg (100). Data points are shown, and averages and standard deviations are indicated by horizontal bars. *, P < 0.001 compared to the vehicle group (one-way ANOVA with Tukey's multiple-comparison test). For comparisons between the indicated groups (one-way ANOVA with Tukey's multiple-comparison test), statistical significance is indicated as follows: **, P < 0.01; ***, P < 0.001; and ****, P < 0.0001.

Article Snippet: E. faecalis strain V583 was used for the in vitro stationary-phase and biofilm killing experiments as well as the in vivo peritoneal septicemia model. Bacterial strains were obtained through the ATCC or BEI Resources or from academic labs (see Table S1 in the supplemental material).

Techniques: In Vivo, Infection, Comparison

Journal: Antimicrobial Agents and Chemotherapy

Article Title: In Vivo and In Vitro Effects of a ClpP-Activating Antibiotic against Vancomycin-Resistant Enterococci

doi: 10.1128/AAC.00424-18

Figure Lengend Snippet: V583 MICs and treatment concentrations for in vitro experiments

Article Snippet: E. faecalis strain V583 was used for the in vitro stationary-phase and biofilm killing experiments as well as the in vivo peritoneal septicemia model. Bacterial strains were obtained through the ATCC or BEI Resources or from academic labs (see Table S1 in the supplemental material).

Techniques: In Vitro, Glycoproteomics