Journal: Nature Communications

Article Title: Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria

doi: 10.1038/s41467-017-02123-w

Figure Lengend Snippet: Mouse efficacy models. a MRSA thigh infection model. Colony forming units (CFU) in neutropenic mice infected in each thigh with MRSA, followed 2 h later by a single subcutaneous dose of antibiotic at concentrations indicated, with sacrifice and bacterial load determination in homogenised thighs at 24 h post treatment (26 h post infection): n = 10 (five mice per group, two thighs per mouse; errors are mean ± SEM). A significant difference was found between saline at 26 h and vancomycin 1 at 200 mg kg −1 ( p < 0.0001), and vancapticin 19 at both 25 mg kg −1 ( p < 0.0001) and 5 mg kg −1 ( p = 0.0011). No statistical difference was found for vancomycin 1 at 25 mg kg −1 or vancapticin 24 at 25 mg kg -1 compared to saline. Vancapticin 19 at 25 mg kg -1 also showed a significant reduction compared to the initial t = 2 h baseline inoculum ( p = 0.0014) whereas vancomycin 1 at 200 mg kg -1 was not statistically significant. Statistical analysis done using Graph Pad, 1-way ANOVA, Bonferroni post-test. b S. pneumoniae lung infection LD 90 . Survival of healthy mice infected with a lethal intratracheal dose of S. pneumoniae ATCC6301 followed 2 h later by a single subcutaneous dose of antibiotic at 25 mg kg -1 ( n = 10 mice per group). c – e Bioluminescent MSSA intraperitoneal model. Neutropenic mice were injected intraperitoneally with 2.5 × 10 7 CFU bioluminescent MSSA Xen-29 (possessing a stable copy of the Photorhabdus luminescens lux operon on the bacterial chromosome) then treated after 0.5 h with subcutaneous doses of saline, 200 mg kg −1 vancomycin, 50 mg kg −1 daptomycin, 25 mg kg −1 19 or 25 mg kg −1 24 ( n = 5 mice per group). c Changes in total flux levels. Variations in bioluminescence were measured at T = 0, 1, 3, 6 and 9 h, quantified with the IVIS Living Image software where the total flux (number of photons/second) was calculated by a user defined region of interest (ROI) covering the infection sites. The saline treated group showed a large increase in the total flux, particularly after 3 h ( T = 3 h). Daptomycin, vancomycin and 19 treated groups showed a progressive reduction in the bioluminescence signal 1 h after inoculation, while the signal detected from 24 increased slightly. All antibiotic administered groups showed reduced bioluminescence signal at T = 9 h compared to immediately after inoculation ( p < 0.001 for all groups; errors are mean ± S.D). d Changes in CFU per spleen after 9 h. Individual spleens were homogenised and diluted for plating. The calculated CFU/spleen counts for five mice are presented, along with the mean (black bar); errors are mean ± S.D. A significant difference was found between saline and vancomycin 1 , daptomycin 4 and compound 19 ( p < 0.001 for all groups). No statistical difference was found for 24 compared to saline, while this compound was found statistically less efficacious than 1 ( p < 0.01), 4 ( p < 0.001), and 19 ( p < 0.001). Statistical analysis done using Graph Pad, 1-way ANOVA, Bonferroni post-test. e Bioluminescent images at T = 9 h. Bioluminescent imaging of infected mice at T = 9 h using Xenogen IVIS-200 Optical In Vivo Imaging System (PerkinElmer)

Article Snippet: Assay # 608100 S. pneumoniae (ATCC ® 6301 TM ), Infected Lung Model. Groups of 10 male specific-pathogen-free ICR mice weighing 22 ± 2 g were used.

Techniques: Infection, Saline, Injection, Software, Imaging, In Vivo Imaging

Journal:

Article Title: Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

doi: 10.1128/AAC.48.3.961-969.2004

Figure Lengend Snippet: MICs of test compounds

Article Snippet: Furthermore, no activity against S. pneumoniae ATCC 6301 or E. coli ATCC 25922 was observed.

Techniques: