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Application of combination of chelerythrine and polymyxin E in inhibition of polymyxin E drug-resistant bacteria

A technology of chelerythrine and polymyxin, applied in the field of biomedicine, can solve the problem that chelerythrine inhibits mcr-positive bacteria and other problems

Pending Publication Date: 2022-08-09
CHINA AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Up to now, there is no report of chelerythrine inhibiting mcr-positive bacteria

Method used

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  • Application of combination of chelerythrine and polymyxin E in inhibition of polymyxin E drug-resistant bacteria
  • Application of combination of chelerythrine and polymyxin E in inhibition of polymyxin E drug-resistant bacteria
  • Application of combination of chelerythrine and polymyxin E in inhibition of polymyxin E drug-resistant bacteria

Examples

Experimental program
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Effect test

preparation example Construction

[0027] The preparation method of the culture medium involved in the following examples is as follows:

[0028] MH liquid culture medium: add 25 g of MH broth medium (Beijing Luqiao Technology Co., Ltd.) to an appropriate amount of distilled water, then dilute to 500 mL with distilled water, sterilize by autoclaving at 121° C. for 20 min, and cool.

[0029] mcr-1 positive Escherichia coli ZJ807 is described in the following literature: Y Wang, GB Tian, ​​R Zhang, Y Shen, JM Tyrrell, X Huang, H Zhou, L Lei, HY Li, Y Doi. Supplementary material: Prevalence, risk factors , outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: anepidemiological and clinical study. The Lancet Infectious Diseases. 2017. The genome sequence of mcr-1-positive Escherichia coli ZJ807 has been uploaded to NCBI, BioSample Accession Number : SAMN05437814. mcr-1 positive Escherichia coli ZJ807 is a polymyxin E-resistant bacteria.

[0030] mcr-8...

Embodiment 1

[0032] Embodiment 1, adopt the checkerboard method to detect the minimum inhibitory concentration of chelerythrine combined with polymyxin E to polymyxin E-resistant bacteria

[0033] According to the CLSI M27-A3 drug susceptibility test standard, the checkerboard method was used to detect the effect of chelerythrine alone, polymyxin E alone and "chelerythrine and polymyxin E combined" on polymyxin E Antibacterial activity of drug-resistant bacteria (mcr-1-positive Escherichia coli ZJ807, mcr-8-positive Klebsiella pneumoniae KP91, or mcr-9-positive Salmonella SLM183), thereby obtaining minimal antibacterial activity against polymyxin E-resistant bacteria concentration. Specific steps are as follows:

[0034] 1. Take the polymyxin E-resistant bacteria liquid that has grown to the logarithmic growth phase, first adjust it to McFarland 0.5 with a McFarland turbidimeter, and then dilute it with MH broth medium 100 times to obtain polymyxins E-resistant bacteria dilution. In the...

Embodiment 2

[0050] Example 2. Time-kill curve of chelerythrine combined with polymyxin E against polymyxin E-resistant bacteria

[0051] Polymyxin E-resistant bacteria were mcr-1 positive Escherichia coli ZJ807, mcr-8 positive Klebsiella pneumoniae KP91 or mcr-9 positive Salmonella SLM183.

[0052] 1. Take the polymyxin E-resistant bacteria solution that has grown to the logarithmic growth phase, and adjust it to McFarland 0.5 with a McFarland turbidimeter to obtain a polymyxin E-resistant bacteria dilution. In the dilution of colistin-E-resistant bacteria, the concentration of colistin-E-resistant bacteria is about 1 × 10 6 CFU / mL.

[0053] 2. Take 12 test tubes, add 2970 μL MH liquid medium and 30 μL polymyxin E-resistant bacteria dilution to each, and mix well; then 12 test tubes are randomly divided into chelerythrine group, polymyxin group Group E, the combined group and the blank group of 4 groups, each with 3 test tubes, were treated as follows:

[0054] The chelerythrine group:...

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Abstract

The invention discloses application of combination of chelerythrine and polymyxin E in inhibition of polymyxin E drug-resistant bacteria. The polymyxin E drug-resistant bacteria are mcr positive bacteria. Experiments prove that chelerythrine can cooperate with polymyxin E to inhibit (such as mcr-1 positive escherichia coli ZJ807, mcr-8 positive klebsiella pneumoniae KP91 and mcr-9 positive salmonella SLM183), and the drug resistance to the polymyxin E is reversed while the use amount of the polymyxin E is reduced. The chelerythrine can recover the inhibition effect of the polymyxin E on the drug-resistant bacteria of the polymyxin E. The method has an important application value.

Description

technical field [0001] The invention belongs to the field of biomedicine, and particularly relates to the application of chelerythrine combined with polymyxin E in inhibiting polymyxin E-resistant bacteria, wherein the polymyxin E-resistant bacteria are mcr-positive bacteria. Background technique [0002] Polymyxin is a polycationic antibacterial peptide, which has a strong and rapid bactericidal effect on most Gram-negative bacteria. The antibacterial mechanism of polymyxin is that it can combine with negatively charged LPS in the cell membrane of Gram-negative bacteria, resulting in changes in the permeability of bacterial cell membranes, resulting in the leakage of important substances such as bacterial nucleic acids and amino acids, thereby inhibiting bacterial growth and leading to bacterial death. . In recent years, with the increasingly severe forms of bacterial drug resistance, polymyxin has become one of the "last lines of defense" in the clinical treatment of mult...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/12A61K31/4741A61P31/04
CPCA61K38/12A61K31/4741A61P31/04A61K2300/00Y02A50/30
Inventor 吴聪明汪洋宋黄威王雪杨张慕琛邹之宇杨思源刘德俊沈应博沈建忠
Owner CHINA AGRI UNIV
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