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Application of Hydroquinolins in Enhancing the Sensitivity of Bacteria to Colistin

A polymyxin and compound technology, applied in the new application field of compounds, can solve problems such as resensitization

Active Publication Date: 2019-10-11
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there is currently no information suggesting or reporting that hydroquinolins have the effect of resensitizing MCR-1-positive resistant bacteria to polymyxins

Method used

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  • Application of Hydroquinolins in Enhancing the Sensitivity of Bacteria to Colistin
  • Application of Hydroquinolins in Enhancing the Sensitivity of Bacteria to Colistin
  • Application of Hydroquinolins in Enhancing the Sensitivity of Bacteria to Colistin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] The influence of embodiment 1 hydroquinolins compound on bacterial growth

[0047] 1) Bacterial culture: 4 strains of MCR-1 positive drug-resistant bacteria and Escherichia coli standard strain ATCC25922 were selected as experiments. After the solid LB plate was revived, single colonies were selected and cultured overnight with MH medium to enrich the bacteria.

[0048] 2) Bacterial suspension preparation: Prepare a 0.5 McFarland turbidity bacterial suspension with physiological saline, and dilute it with MH culture medium 1:100 to make the bacterial content 1.5×10 6 cfu / ml, inoculate 50 μl per well in a 96-well plate.

[0049] 3) Add 50 μl of various hydroquinolin compounds (as shown in Table 1) with a concentration of 100 μM in a 96-well plate, and inoculate 4 strains of MCR-1-positive drug-resistant bacteria and ATCC25922 into 96 wells, and each strain of bacteria Inoculate 50 μl of bacterial solution, so that the total volume of each well is 100 μl, and the concen...

Embodiment 2

[0055] Example 2 High Concentration Hydroquinolins Enhance Bacteria's Effect on Colistin Sensitivity

[0056] 1) Bacterial culture: 4 strains of MCR-1-positive drug-resistant bacteria were selected as experimental strains, and Escherichia coli standard strain ATCC25922 was used as quality control bacteria. After the solid LB plate was revived, single colonies were selected and cultured overnight with MH medium to enrich the bacteria.

[0057] 2) Bacterial suspension preparation: Prepare a 0.5 McFarland turbidity bacterial suspension with physiological saline, and dilute it with MH culture medium 1:100 to make the bacterial content 1.5×10 6 cfu / ml, inoculate 50 μl per well in a 96-well plate.

[0058]3) Add 25 μl of polymyxin with a concentration of 64 mg / ml to the 96-well plate. Then continue to add 25 μl of various hydroquinolins (see Table 1) at a concentration of 200 μM in the 96-well plate, and inoculate 4 strains of MCR-1 positive drug-resistant bacteria and ATCC25922 i...

Embodiment 3

[0061] Example 3 Low-concentration hydroquinolins enhance the effect of bacteria on polymyxin sensitivity

[0062] 1) Bacterial culture: select 4 strains of MCR-1-positive drug-resistant bacteria and Escherichia coli standard strain ATCC25922 (without mcr-1 gene) as the experimental strains, and after recovering with solid LB plates, select single colonies respectively, and use MH medium overnight Cultivate, enrich.

[0063] 2) Bacterial suspension preparation: Prepare a 0.5 McFarland turbidity bacterial suspension with physiological saline, and dilute it with MH culture medium 1:100 to make the bacterial content 1.5×10 6 cfu / ml, inoculate 50 μl per well in a 96-well plate.

[0064] 3) Dilute each hydroquinolin compound of the present invention and polymyxin (6 dilutions, 2 times of MIC value, 1 time, 1 / 2, 1 / 4, 1 / 8, 1 / 16 concentration respectively) dilution). The horizontal direction is the direction of the descending gradient of the antibiotic, and the vertical direction i...

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Abstract

The invention discloses application of hydroquinoline compounds in enhancing the sensitivity of bacteria to polymyxin. Experiments on the minimum inhibitory concentration of multiple MCR-1 positive drug resistant bacteria find that the hydroquinoline compounds can re-sensitize MCR-1 positive drug resistant bacteria to polymyxin, which provides a strong theoretical basis and practical basis for thefurther development of new strategies for treating MCR-1 positive drug resistant bacteria and for promoting the clinical transformation of therapeutic drugs. The application has important research and development value and development significance.

Description

technical field [0001] The invention relates to a new application of a compound, in particular to the application of a hydroquinolin compound in enhancing the polymyxin sensitivity of MCR-1 positive drug-resistant bacteria. Background technique [0002] The mcr-1 gene (mobile colistin resistance, mobile colistin resistance gene) encodes the MCR-1 enzyme, which has phosphoethanol aminotransferase activity and can catalyze the transfer of phosphatidylethanolamine (PEA) to the outer membrane of cells. The fourth phosphate group of lipid A changes the structure of lipid A in the outer membrane of the cell, thereby reducing the affinity between polymyxin and lipopolysaccharide, changing the target of polymyxin, and then mediating resistance. medicine. Moreover, Feng Youjun et al. found that the correct expression of the transmembrane region and five key amino acids (E246, T285, H395, 465D, 466H) of MCR-1 is the basis for its activity of phosphoethanol aminotransferase. [0003]...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4709A61K31/47A61K38/12A61P31/04
Inventor 柏川田国宝劳楚瑜钟兰兰温馨
Owner SUN YAT SEN UNIV