colistin resistant 3 escherichia coli atcc 25922 e coli b2 mcr 1  (ATCC)

Journal: Research in microbiology

Article Title: Susceptibility of colistin-resistant pathogens to predatory bacteria

doi: 10.1016/j.resmic.2017.09.001

Figure Lengend Snippet: Reduction in planktonic prey cell viability (log 10 CFU/ml) following 24 or 48 (*) h of incubation.

Article Snippet: As the factors impacting prey specificity are not known at this point, we can only speculate on the basis of the inability of M. aeruginosavorus to prey on the E. coli strain used in this study. table ft1 table-wrap mode="anchored" t5 caption a7 Prey Predator B. bacteriovorus 109J B. bacteriovorus HD100 M. aeruginosavorus ARL-13 A. baumannii ATCC 17978 3.17 ± 1.00 3.67 ± 0.32 0.24* ± 0.39 A. baumannii ATCC 17978 pMQ124XLAB1-mcr-1 2.99 ± 0.33 3.71 ± 0.26 0.09* ± 0.12 E. coli ATCC 25922 4.78 ± 0.91 4.56 ± 0.67 0.17* ± 0.30 E. coli ATCC 25922 pMQ124-mcr-1 5.09 ± 0.87 4.90 ± 0.76 0.18* ± 0.18 K. pneumoniae ATCC 13883 3.06 ± 0.46 4.53 ± 0.17 3.40 ± 0.61 K. pneumoniae ATCC 13883 pMQ124-mcr-1 3.66 ± 1.04 4.29 ± 0.92 2.76 ± 0.21 P. aeruginosa ATCC 47085 2.52 ± 0.51 4.53 ± 0.17 2.50* ± 0.47 P. aeruginosa ATCC 47085 pMQ124-mcr-1 3.13 ± 0.12 4.77 ± 0.27 2.14* ± 0.55 Open in a separate window Co-cultures were prepared by adding ~1 × 10 8 CFU/ml prey cells to harvested predator cells (~1 × 10 8 PFU/ml for B. bacteriovorus and ~1 × 10 7 PFU/ml for M. aeruginosavorus ) or predator free control.

Techniques: Incubation

Journal: Research in microbiology

Article Title: Susceptibility of colistin-resistant pathogens to predatory bacteria

doi: 10.1016/j.resmic.2017.09.001

Figure Lengend Snippet: Removal of biofilms by B. bacteriovorus. Biofilms of A. baumannii (A) and E. coli (B) were developed in 96-well plates for 24 h (preformed biofilm) following a 24 h incubation period with B. bacteriovorus 109J (109J), B. bacteriovorus HD100 (HD100), or predator free control (control). Biofilms were rinsed and stained with CV and the amount of CV staining was quantified at 600 nm (A600). Each value represents the mean of 12 wells. Error bars are shown as one-standard deviation. Numbers above the bars represent the average percent reduction in biofilm biomass compared to the control.

Article Snippet: As the factors impacting prey specificity are not known at this point, we can only speculate on the basis of the inability of M. aeruginosavorus to prey on the E. coli strain used in this study. table ft1 table-wrap mode="anchored" t5 caption a7 Prey Predator B. bacteriovorus 109J B. bacteriovorus HD100 M. aeruginosavorus ARL-13 A. baumannii ATCC 17978 3.17 ± 1.00 3.67 ± 0.32 0.24* ± 0.39 A. baumannii ATCC 17978 pMQ124XLAB1-mcr-1 2.99 ± 0.33 3.71 ± 0.26 0.09* ± 0.12 E. coli ATCC 25922 4.78 ± 0.91 4.56 ± 0.67 0.17* ± 0.30 E. coli ATCC 25922 pMQ124-mcr-1 5.09 ± 0.87 4.90 ± 0.76 0.18* ± 0.18 K. pneumoniae ATCC 13883 3.06 ± 0.46 4.53 ± 0.17 3.40 ± 0.61 K. pneumoniae ATCC 13883 pMQ124-mcr-1 3.66 ± 1.04 4.29 ± 0.92 2.76 ± 0.21 P. aeruginosa ATCC 47085 2.52 ± 0.51 4.53 ± 0.17 2.50* ± 0.47 P. aeruginosa ATCC 47085 pMQ124-mcr-1 3.13 ± 0.12 4.77 ± 0.27 2.14* ± 0.55 Open in a separate window Co-cultures were prepared by adding ~1 × 10 8 CFU/ml prey cells to harvested predator cells (~1 × 10 8 PFU/ml for B. bacteriovorus and ~1 × 10 7 PFU/ml for M. aeruginosavorus ) or predator free control.

Techniques: Incubation, Control, Staining, Standard Deviation

Journal: Research in microbiology

Article Title: Susceptibility of colistin-resistant pathogens to predatory bacteria

doi: 10.1016/j.resmic.2017.09.001

Figure Lengend Snippet: Reduction in planktonic prey cell viability (log 10 CFU/ml) following 24 or 48 (*) h of incubation.

Article Snippet: E. coli ATCC 25922 pMQ124-mcr-1 , 5.09 ± 0.87 , 4.90 ± 0.76 , 0.18* ± 0.18.

Techniques: Incubation

Journal: Research in microbiology

Article Title: Susceptibility of colistin-resistant pathogens to predatory bacteria

doi: 10.1016/j.resmic.2017.09.001

Figure Lengend Snippet: Removal of biofilms by B. bacteriovorus. Biofilms of A. baumannii (A) and E. coli (B) were developed in 96-well plates for 24 h (preformed biofilm) following a 24 h incubation period with B. bacteriovorus 109J (109J), B. bacteriovorus HD100 (HD100), or predator free control (control). Biofilms were rinsed and stained with CV and the amount of CV staining was quantified at 600 nm (A600). Each value represents the mean of 12 wells. Error bars are shown as one-standard deviation. Numbers above the bars represent the average percent reduction in biofilm biomass compared to the control.

Article Snippet: E. coli ATCC 25922 pMQ124-mcr-1 , 5.09 ± 0.87 , 4.90 ± 0.76 , 0.18* ± 0.18.

Techniques: Incubation, Control, Staining, Standard Deviation

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: MIC (μg/mL (fold reduction)) of colistin with in-house library adjuvants dosed at 60 μM.

Article Snippet: Using this same methodology, we then employed both 5-hydroxytryptamine and 5-methoxytryptamine to afford the corresponding indole ring substitution in final products 16 and 17 , which were both upwards of eight-fold less active than 2 . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 1. caption a7 Reaction scheme and structures of compounds 8 through 17 . (a): Br 2 , CHCl 3 , 2h, RT. (b): RCH 2 NH 2 , K 2 CO 3 , DMF, 18h, RT. table ft1 table-wrap mode="anchored" t5 Table 2. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 No compound 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL 8 (23.8 μg/mL) 0.5 (2048) 0.5 (2048) 0.5 (32) 0.5 (16) 9 (25.5 μg/mL) 2 (512) 0.25 (4096) 0.5 (32) 0.5 (16) 10 (21.7 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 11 (21.5 μg/mL) 512 (2) 512 (2) 16 (0) 8 (0) 12 (22.4 μg/mL) 1024 (0) 512 (2) 16 (0) 8 (0) 13 (23.0 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 14 (23.8 μg/mL) 0.5 (2048) 0.25 (4096) 0.5 (32) 0.5 (16) 15 (23.8 μg/mL) 4 (256) 0.5 (2048) 0.5 (32) 1 (8) 16 (25.6 μg/mL) 256 (4) 128 (8) 4 (4) 2 (4) 17 (26.5 μg/mL) 8 (128) 8 (128) 2 (8) 4 (2) 19 (25.7 μg/mL) 32 (32) 64 (16) 2 (8) 2 (4) 24 (25.7 μg/mL) 2 (512) 16 (64) 0.5 (32) 1 (8) 25 (25.5 μg/mL) 4 (256) 2 (512) 0.5 (32) 1 (8) 29a (25.5 μg/mL) 256 (4) 1024 (0) 16 (0) 8 (0) 29b (28.0 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) 29c (30.1 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Initial screen of head-group substituted analogs dosed at 60 μM with colistin given as MIC (μg/mL (fold reduction)).

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: Initial screen of head-group substituted analogs dosed at 60 μM with colistin given as MIC (μg/mL (fold reduction)).

Article Snippet: Using this same methodology, we then employed both 5-hydroxytryptamine and 5-methoxytryptamine to afford the corresponding indole ring substitution in final products 16 and 17 , which were both upwards of eight-fold less active than 2 . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 1. caption a7 Reaction scheme and structures of compounds 8 through 17 . (a): Br 2 , CHCl 3 , 2h, RT. (b): RCH 2 NH 2 , K 2 CO 3 , DMF, 18h, RT. table ft1 table-wrap mode="anchored" t5 Table 2. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 No compound 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL 8 (23.8 μg/mL) 0.5 (2048) 0.5 (2048) 0.5 (32) 0.5 (16) 9 (25.5 μg/mL) 2 (512) 0.25 (4096) 0.5 (32) 0.5 (16) 10 (21.7 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 11 (21.5 μg/mL) 512 (2) 512 (2) 16 (0) 8 (0) 12 (22.4 μg/mL) 1024 (0) 512 (2) 16 (0) 8 (0) 13 (23.0 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 14 (23.8 μg/mL) 0.5 (2048) 0.25 (4096) 0.5 (32) 0.5 (16) 15 (23.8 μg/mL) 4 (256) 0.5 (2048) 0.5 (32) 1 (8) 16 (25.6 μg/mL) 256 (4) 128 (8) 4 (4) 2 (4) 17 (26.5 μg/mL) 8 (128) 8 (128) 2 (8) 4 (2) 19 (25.7 μg/mL) 32 (32) 64 (16) 2 (8) 2 (4) 24 (25.7 μg/mL) 2 (512) 16 (64) 0.5 (32) 1 (8) 25 (25.5 μg/mL) 4 (256) 2 (512) 0.5 (32) 1 (8) 29a (25.5 μg/mL) 256 (4) 1024 (0) 16 (0) 8 (0) 29b (28.0 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) 29c (30.1 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Initial screen of head-group substituted analogs dosed at 60 μM with colistin given as MIC (μg/mL (fold reduction)).

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: Colistin MIC (μg/mL (fold reduction)) of col R strains co-challenged with tail-group substituted and shortened analogs of 2 dosed at 60 μM.

Article Snippet: Using this same methodology, we then employed both 5-hydroxytryptamine and 5-methoxytryptamine to afford the corresponding indole ring substitution in final products 16 and 17 , which were both upwards of eight-fold less active than 2 . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 1. caption a7 Reaction scheme and structures of compounds 8 through 17 . (a): Br 2 , CHCl 3 , 2h, RT. (b): RCH 2 NH 2 , K 2 CO 3 , DMF, 18h, RT. table ft1 table-wrap mode="anchored" t5 Table 2. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 No compound 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL 8 (23.8 μg/mL) 0.5 (2048) 0.5 (2048) 0.5 (32) 0.5 (16) 9 (25.5 μg/mL) 2 (512) 0.25 (4096) 0.5 (32) 0.5 (16) 10 (21.7 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 11 (21.5 μg/mL) 512 (2) 512 (2) 16 (0) 8 (0) 12 (22.4 μg/mL) 1024 (0) 512 (2) 16 (0) 8 (0) 13 (23.0 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 14 (23.8 μg/mL) 0.5 (2048) 0.25 (4096) 0.5 (32) 0.5 (16) 15 (23.8 μg/mL) 4 (256) 0.5 (2048) 0.5 (32) 1 (8) 16 (25.6 μg/mL) 256 (4) 128 (8) 4 (4) 2 (4) 17 (26.5 μg/mL) 8 (128) 8 (128) 2 (8) 4 (2) 19 (25.7 μg/mL) 32 (32) 64 (16) 2 (8) 2 (4) 24 (25.7 μg/mL) 2 (512) 16 (64) 0.5 (32) 1 (8) 25 (25.5 μg/mL) 4 (256) 2 (512) 0.5 (32) 1 (8) 29a (25.5 μg/mL) 256 (4) 1024 (0) 16 (0) 8 (0) 29b (28.0 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) 29c (30.1 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Initial screen of head-group substituted analogs dosed at 60 μM with colistin given as MIC (μg/mL (fold reduction)).

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: MIC (μg/mL (fold reduction)) of colistin with adjuvants dosed at 60 μM against nine Gram-negative strains.

Article Snippet: Using this same methodology, we then employed both 5-hydroxytryptamine and 5-methoxytryptamine to afford the corresponding indole ring substitution in final products 16 and 17 , which were both upwards of eight-fold less active than 2 . fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 1. caption a7 Reaction scheme and structures of compounds 8 through 17 . (a): Br 2 , CHCl 3 , 2h, RT. (b): RCH 2 NH 2 , K 2 CO 3 , DMF, 18h, RT. table ft1 table-wrap mode="anchored" t5 Table 2. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 No compound 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL 8 (23.8 μg/mL) 0.5 (2048) 0.5 (2048) 0.5 (32) 0.5 (16) 9 (25.5 μg/mL) 2 (512) 0.25 (4096) 0.5 (32) 0.5 (16) 10 (21.7 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 11 (21.5 μg/mL) 512 (2) 512 (2) 16 (0) 8 (0) 12 (22.4 μg/mL) 1024 (0) 512 (2) 16 (0) 8 (0) 13 (23.0 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 14 (23.8 μg/mL) 0.5 (2048) 0.25 (4096) 0.5 (32) 0.5 (16) 15 (23.8 μg/mL) 4 (256) 0.5 (2048) 0.5 (32) 1 (8) 16 (25.6 μg/mL) 256 (4) 128 (8) 4 (4) 2 (4) 17 (26.5 μg/mL) 8 (128) 8 (128) 2 (8) 4 (2) 19 (25.7 μg/mL) 32 (32) 64 (16) 2 (8) 2 (4) 24 (25.7 μg/mL) 2 (512) 16 (64) 0.5 (32) 1 (8) 25 (25.5 μg/mL) 4 (256) 2 (512) 0.5 (32) 1 (8) 29a (25.5 μg/mL) 256 (4) 1024 (0) 16 (0) 8 (0) 29b (28.0 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) 29c (30.1 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Initial screen of head-group substituted analogs dosed at 60 μM with colistin given as MIC (μg/mL (fold reduction)).

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: MIC (μg/mL (fold reduction)) of colistin with in-house library adjuvants dosed at 60 μM.

Article Snippet: Isolated activity was seen with 37 in K. pneumoniae B9, returning a colistin MIC of 1 μg/mL (1024 fold reduction) when dosed at 60 μM, while remaining inactive in other Gram-negative strains. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 3. caption a7 Reaction scheme and structures of compounds 30 through 39 ; (a): RCOCl, TEA, DMF; (b): RCOOH, TEA, PyBOP, DMF. table ft1 table-wrap mode="anchored" t5 Table 3. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL No compound 30 (16.2 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 31 (17.3 μg/mL) 64 (16) 128 (8) 8 (2) 4 (2) 32 (24.7 μg/mL) 16 (64) 2 (512) 1 (16) 4 (2) 33 (25.7 μg/mL) 32 (32) 2 (512) 1 (16) 4 (2) 34 (20.0 μg/mL) 64 (16) 16 (64) 8 (2) 8 (0) 35 (21.0 μg/mL) 16 (64) 8 (128) 4 (4) 4 (2) 36 (25.4 μg/mL) 128 (8) 8 (128) 16 (0) 8 (0) 37 (20.7 μg/mL) 64 (16) 1 (1024) 8 (2) 4 (2) 38 (20.7 μg/mL) 256 (4) 128 (8) 16 (0) 8 (0) 39 (15.9 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 41a (25.5 μg/mL) 32 (32) 4 (256) 1 (16) 4 (2) 41b (28.0 μg/mL) 64 (16) 64 (16) 8 (2) 8 (0) 41c (30.1 μg/mL) 128 (8) 64 (16) 8 (2) 8 (0) 44 (30.3 μg/mL) 8 (128) 0.5 (2048) 1 (16) 2 (4) 45 (22.8 μg/mL) 16 (64) 0.5 (2048) 1 (16) 4 (2) 46 (20.7 μg/mL) 32 (32) 32 (32) 16 (0) 8 (0) 47 (29.5 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Colistin MIC (μg/mL (fold reduction)) of col R strains co-challenged with tail-group substituted and shortened analogs of 2 dosed at 60 μM.

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: Initial screen of head-group substituted analogs dosed at 60 μM with colistin given as MIC (μg/mL (fold reduction)).

Article Snippet: Isolated activity was seen with 37 in K. pneumoniae B9, returning a colistin MIC of 1 μg/mL (1024 fold reduction) when dosed at 60 μM, while remaining inactive in other Gram-negative strains. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 3. caption a7 Reaction scheme and structures of compounds 30 through 39 ; (a): RCOCl, TEA, DMF; (b): RCOOH, TEA, PyBOP, DMF. table ft1 table-wrap mode="anchored" t5 Table 3. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL No compound 30 (16.2 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 31 (17.3 μg/mL) 64 (16) 128 (8) 8 (2) 4 (2) 32 (24.7 μg/mL) 16 (64) 2 (512) 1 (16) 4 (2) 33 (25.7 μg/mL) 32 (32) 2 (512) 1 (16) 4 (2) 34 (20.0 μg/mL) 64 (16) 16 (64) 8 (2) 8 (0) 35 (21.0 μg/mL) 16 (64) 8 (128) 4 (4) 4 (2) 36 (25.4 μg/mL) 128 (8) 8 (128) 16 (0) 8 (0) 37 (20.7 μg/mL) 64 (16) 1 (1024) 8 (2) 4 (2) 38 (20.7 μg/mL) 256 (4) 128 (8) 16 (0) 8 (0) 39 (15.9 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 41a (25.5 μg/mL) 32 (32) 4 (256) 1 (16) 4 (2) 41b (28.0 μg/mL) 64 (16) 64 (16) 8 (2) 8 (0) 41c (30.1 μg/mL) 128 (8) 64 (16) 8 (2) 8 (0) 44 (30.3 μg/mL) 8 (128) 0.5 (2048) 1 (16) 2 (4) 45 (22.8 μg/mL) 16 (64) 0.5 (2048) 1 (16) 4 (2) 46 (20.7 μg/mL) 32 (32) 32 (32) 16 (0) 8 (0) 47 (29.5 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Colistin MIC (μg/mL (fold reduction)) of col R strains co-challenged with tail-group substituted and shortened analogs of 2 dosed at 60 μM.

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: Colistin MIC (μg/mL (fold reduction)) of col R strains co-challenged with tail-group substituted and shortened analogs of 2 dosed at 60 μM.

Article Snippet: Isolated activity was seen with 37 in K. pneumoniae B9, returning a colistin MIC of 1 μg/mL (1024 fold reduction) when dosed at 60 μM, while remaining inactive in other Gram-negative strains. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 3. caption a7 Reaction scheme and structures of compounds 30 through 39 ; (a): RCOCl, TEA, DMF; (b): RCOOH, TEA, PyBOP, DMF. table ft1 table-wrap mode="anchored" t5 Table 3. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL No compound 30 (16.2 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 31 (17.3 μg/mL) 64 (16) 128 (8) 8 (2) 4 (2) 32 (24.7 μg/mL) 16 (64) 2 (512) 1 (16) 4 (2) 33 (25.7 μg/mL) 32 (32) 2 (512) 1 (16) 4 (2) 34 (20.0 μg/mL) 64 (16) 16 (64) 8 (2) 8 (0) 35 (21.0 μg/mL) 16 (64) 8 (128) 4 (4) 4 (2) 36 (25.4 μg/mL) 128 (8) 8 (128) 16 (0) 8 (0) 37 (20.7 μg/mL) 64 (16) 1 (1024) 8 (2) 4 (2) 38 (20.7 μg/mL) 256 (4) 128 (8) 16 (0) 8 (0) 39 (15.9 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 41a (25.5 μg/mL) 32 (32) 4 (256) 1 (16) 4 (2) 41b (28.0 μg/mL) 64 (16) 64 (16) 8 (2) 8 (0) 41c (30.1 μg/mL) 128 (8) 64 (16) 8 (2) 8 (0) 44 (30.3 μg/mL) 8 (128) 0.5 (2048) 1 (16) 2 (4) 45 (22.8 μg/mL) 16 (64) 0.5 (2048) 1 (16) 4 (2) 46 (20.7 μg/mL) 32 (32) 32 (32) 16 (0) 8 (0) 47 (29.5 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Colistin MIC (μg/mL (fold reduction)) of col R strains co-challenged with tail-group substituted and shortened analogs of 2 dosed at 60 μM.

Techniques:

Journal: Bioorganic & medicinal chemistry

Article Title: Tryptamine Derivatives Disarm Colistin Resistance in Polymyxin-Resistant Gram-negative Bacteria

doi: 10.1016/j.bmc.2019.03.019

Figure Lengend Snippet: MIC (μg/mL (fold reduction)) of colistin with adjuvants dosed at 60 μM against nine Gram-negative strains.

Article Snippet: Isolated activity was seen with 37 in K. pneumoniae B9, returning a colistin MIC of 1 μg/mL (1024 fold reduction) when dosed at 60 μM, while remaining inactive in other Gram-negative strains. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Scheme 3. caption a7 Reaction scheme and structures of compounds 30 through 39 ; (a): RCOCl, TEA, DMF; (b): RCOOH, TEA, PyBOP, DMF. table ft1 table-wrap mode="anchored" t5 Table 3. caption a7 A. baumannii 4106 K. pneumoniae B9 A. baumannii ATCC 17978 + mcr−1 E. coli ATCC 25922 + mcr−1 1024 μg/mL 1024 μg/mL 16 μg/mL 8 μg/mL No compound 30 (16.2 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 31 (17.3 μg/mL) 64 (16) 128 (8) 8 (2) 4 (2) 32 (24.7 μg/mL) 16 (64) 2 (512) 1 (16) 4 (2) 33 (25.7 μg/mL) 32 (32) 2 (512) 1 (16) 4 (2) 34 (20.0 μg/mL) 64 (16) 16 (64) 8 (2) 8 (0) 35 (21.0 μg/mL) 16 (64) 8 (128) 4 (4) 4 (2) 36 (25.4 μg/mL) 128 (8) 8 (128) 16 (0) 8 (0) 37 (20.7 μg/mL) 64 (16) 1 (1024) 8 (2) 4 (2) 38 (20.7 μg/mL) 256 (4) 128 (8) 16 (0) 8 (0) 39 (15.9 μg/mL) 128 (8) 1024 (0) 16 (0) 8 (0) 41a (25.5 μg/mL) 32 (32) 4 (256) 1 (16) 4 (2) 41b (28.0 μg/mL) 64 (16) 64 (16) 8 (2) 8 (0) 41c (30.1 μg/mL) 128 (8) 64 (16) 8 (2) 8 (0) 44 (30.3 μg/mL) 8 (128) 0.5 (2048) 1 (16) 2 (4) 45 (22.8 μg/mL) 16 (64) 0.5 (2048) 1 (16) 4 (2) 46 (20.7 μg/mL) 32 (32) 32 (32) 16 (0) 8 (0) 47 (29.5 μg/mL) 1024 (0) 1024 (0) 16 (0) 8 (0) Open in a separate window Colistin MIC (μg/mL (fold reduction)) of col R strains co-challenged with tail-group substituted and shortened analogs of 2 dosed at 60 μM.

Techniques: