CN111184722A - Application of tetrandrine in preparation of escherichia coli drug-resistant inhibitor - Google Patents
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- CN111184722A CN111184722A CN202010170540.XA CN202010170540A CN111184722A CN 111184722 A CN111184722 A CN 111184722A CN 202010170540 A CN202010170540 A CN 202010170540A CN 111184722 A CN111184722 A CN 111184722A
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- WVTKBKWTSCPRNU-KYJUHHDHSA-N (+)-Tetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-KYJUHHDHSA-N 0.000 title claims abstract description 60
- 241000588724 Escherichia coli Species 0.000 title claims abstract description 56
- 239000003814 drug Substances 0.000 title claims abstract description 51
- 229940079593 drug Drugs 0.000 title claims abstract description 42
- WVTKBKWTSCPRNU-UHFFFAOYSA-N rac-Tetrandrin Natural products O1C(C(=CC=2CCN3C)OC)=CC=2C3CC(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2CC2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 239000003112 inhibitor Substances 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 229940124307 fluoroquinolone Drugs 0.000 claims abstract description 15
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 22
- 206010059866 Drug resistance Diseases 0.000 claims description 15
- SPFYMRJSYKOXGV-UHFFFAOYSA-N Baytril Chemical compound C1CN(CC)CCN1C(C(=C1)F)=CC2=C1C(=O)C(C(O)=O)=CN2C1CC1 SPFYMRJSYKOXGV-UHFFFAOYSA-N 0.000 claims description 14
- 229960000740 enrofloxacin Drugs 0.000 claims description 14
- 229960003405 ciprofloxacin Drugs 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 8
- 230000014509 gene expression Effects 0.000 abstract description 9
- 230000001404 mediated effect Effects 0.000 abstract description 8
- 239000013612 plasmid Substances 0.000 abstract description 8
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 239000003640 drug residue Substances 0.000 abstract description 3
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 230000001580 bacterial effect Effects 0.000 description 15
- 239000007788 liquid Substances 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000001963 growth medium Substances 0.000 description 4
- 238000001179 sorption measurement Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000013642 negative control Substances 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 238000010839 reverse transcription Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 238000010804 cDNA synthesis Methods 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000012154 double-distilled water Substances 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 1
- 241001476742 Escherichia coli IS5 Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 239000006137 Luria-Bertani broth Substances 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000001351 cycling effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000003161 ribonuclease inhibitor Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4748—Quinolines; Isoquinolines forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Organic Chemistry (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
The invention discloses application of tetrandrine in preparation of an escherichia coli drug-resistant inhibitor, and research results show that tetrandrine can obviously reduce the minimum inhibitory concentration of fluoroquinolone drugs escherichia coli with fluoroquinolone drugs and can obviously reduce plasmid-mediated quinolone drug-resistant geneaac(6’)‑Ib‑crThe expression level is obviously reduced, so that the sensitivity of the drug-resistant escherichia coli to the fluoroquinolone can be improved, the drug use level is reduced, the treatment cost is reduced, and the food safety problems such as drug residue and the like are reduced; meanwhile, the tetrandrine is one of the main components of the traditional Chinese medicine, so that the application field of the traditional Chinese medicine is widened, and the market value of the tetrandrine is improved.
Description
Technical Field
The invention belongs to the field of pharmacy, and relates to a new pharmaceutical application of tetrandrine.
Background
The development and application of antibacterial agents have reduced morbidity and mortality in humans and animals, but with the widespread use of antibacterial agents, bacterial resistance has also become more severe. In particular, the drug resistance rate of escherichia coli to quinolone drugs tends to increase year by year. Escherichia coli (Escherichia coli) Is one of the most common pathogenic bacteria harming the health of livestock, poultry and even human beings, and has complex antigenicity and diversityThe serotype of the Chinese traditional medicine is easy to change, the clinical symptoms and pathological changes are easy to change and change, and the Chinese traditional medicine is easy to be complicated with viral diseases and other bacterial diseases, and brings great economic loss to the breeding industry. The mechanism of drug resistance of escherichia coli to fluoroquinolone drugs comprises multiple factors such as target gene mutation, high expression of efflux genes, plasmid-mediated drug resistance and the like, wherein the plasmid-mediated drug resistance is easy to horizontally spread among strains, so that the plasmid-mediated drug resistance has important influence on the drug resistance of the escherichia coli. Therefore, the development of a drug capable of inhibiting plasmid-mediated drug resistance has important social significance and economic value for delaying bacterial drug resistance, reducing the use of antibacterial drugs, reducing the breeding cost and reducing drug residues in animal products and animal excreta.
Disclosure of Invention
The invention aims to search for a high-efficiency and safe bacterial drug resistance inhibitor from traditional Chinese medicines.
In order to achieve the purpose, the invention provides the following technical scheme:
use of tetrandrine in preparation of Escherichia coli (E. coli)Escherichia coli) Application in drug resistance inhibitor.
Further, the Escherichia coli (E.coli) (II)Escherichia coli) Is a strain of fluoroquinolone resistant drugs.
Further, the fluoroquinolone medicine is ciprofloxacin or enrofloxacin.
The invention has the beneficial effects that: the invention discloses application of tetrandrine in preparation of an escherichia coli drug-resistant inhibitor, and research results show that tetrandrine can obviously reduce the minimum inhibitory concentration of fluoroquinolone drugs escherichia coli with fluoroquinolone drugs and can obviously reduce plasmid-mediated quinolone drug-resistant geneaac(6’)-Ib-crThe expression level is obviously reduced, so that the sensitivity of the drug-resistant escherichia coli to the fluoroquinolone can be improved, the drug use level is reduced, the treatment cost is reduced, and the food safety problems such as drug residue and the like are reduced; meanwhile, the tetrandrine is one of the main components of the traditional Chinese medicine, so that the application field of the traditional Chinese medicine is widened, and the market value of the tetrandrine is improved.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in detail by the following specific embodiments.
Coli ATCC25922 used in the examples was a non-drug resistant standard strain purchased from the chinese veterinary institute.
Escherichia coli 12-2 and 16-1, which were fluoroquinolone-resistant drugs used in the examples, were isolated, identified and preserved in the research laboratory of the inventors, and were obtained by the public through the department of pharmacy of the institute of animal science, Rongchang school, university in southwest.
1. Determination of Minimum Inhibitory Concentration (MIC) of fluoroquinolone drugs on escherichia coli
Quality control bacteria: escherichia coli ATCC 25922; the test bacteria: escherichia coli 12-2, 16-1
The tests were carried out by determining the MIC of enrofloxacin and ciprofloxacin for the strain using the broth microdilution method, according to the method of the American society for clinical and laboratory standards CLSI2013, taking the procedures for determining the MIC of enrofloxacin for Escherichia coli as an example, and the following procedures are as follows:
① in a clean bench, picking out single colony growing well on the plate, transferring to 5ml nutrient broth liquid culture medium, and shake culturing for 5h in 37 deg.C gas bath constant temperature oscillator.
② in a clean bench, the bacterial liquid is diluted with sterilized normal saline to a bacterial liquid concentration of about 1.5 × 108CFU/ml, namely measuring the absorbance OD660 at 660nm by using an ultraviolet spectrophotometer to be 0.08-0.13, and preparing the bacterial liquid for later use.
③ the sterilized disposable 96-well plate was taken out, and the date, bacterial name, drug name and concentration were recorded with a marker pen.
④ adding broth, adding 40mL MH broth from 1-10 holes, adding 40 μ L diluted enrofloxacin liquid with concentration of 1280 μ g/mL into the 1 st hole, sucking by pipette, mixing, sucking 40 μ L to the 2 nd, 3 rd, 4 th, 5 th, 6 th and 7 th holes, mixing, sucking 40 μ L to the 9 th hole as the liquid medicine control, and adding no liquid medicine into the 8 th and 10 th holes.
⑤ adding bacterial liquid, diluting the bacterial liquid in step ② according to 100 mu L of bacterial liquid and 10mLMH broth, and adding 40 mu L of bacterial liquid prepared by MH broth into the diluted bacterial liquid from 8, 7, 6, 5, 4, 3, 2 and 1 holes respectively.
At this time, the enrofloxacin concentrations in the first 7 wells were, in order: 320. 160, 80, 40, 20, 10, 5 mug/ml. The concentration of Escherichia coli is 5 × 105CFU/ml. The 8 th well was a positive control (control for inoculum), the 9 th well was a control for drug (negative control), and the 10 th well was a control for broth (control for blank), and the assay was performed in triplicate. The minimum drug concentration for aseptic growth was taken as the MIC of the drug for this strain.
The MIC values of ciprofloxacin, enrofloxacin and tetrandrine to each strain are finally measured and shown in table 1, and the MIC values of ciprofloxacin and enrofloxacin to 12-2 and 16-1 are more than 4 times of the MIC values of standard bacteria ATCC25922, so that the two strains are indicated to have drug resistance to ciprofloxacin and enrofloxacin.
TABLE 1 MIC of drugs to Strain (μ g/mL)
| Bacterial strains | Ciprofloxacin | Enrofloxacin | Tetrandrine |
| 12-2 | 80 | 80 | 512 |
| 16-1 | 2 | 2 | 512 |
| ATCC25922 | 0.078 | 0.062 | 320 |
2. Continuous subculturing of drug-resistant escherichia coli by using tetrandrine-containing culture medium
Taking Escherichia coli 12-2 and 16-1 as test bacteria, adding tetrandrine with 1/4 × MIC concentration corresponding to the strain in the nutrient broth to culture drug-resistant Escherichia coli 12-2 and 16-1, continuously culturing for 4 generations, taking the nutrient broth without tetrandrine to culture corresponding strain as negative control, and finally determining MIC values of enrofloxacin and ciprofloxacin to cultured Escherichia coli.
The MIC values of the enrofloxacin and the ciprofloxacin which are not changed for the escherichia coli of the negative control group are reduced after the escherichia coli is cultured by the culture medium containing tetrandrine, and the specific results are shown in Table 2. After the continuous culture for 4 generations in the culture medium containing tetrandrine, the MIC values of the fluoroquinolone drugs ciprofloxacin and enrofloxacin to the drug-resistant bacteria 12-2 and 16-1 are obviously reduced, which indicates that the tetrandrine has a certain reversal effect on the drug resistance of escherichia coli to the fluoroquinolone drugs.
TABLE 2 MIC of drugs against strains after subculture (μ g/mL)
| Bacterial strains | Ciprofloxacin | Enrofloxacin |
| 12-2 | 20 | 8 |
| 16-1 | 0.3 | 0.5 |
3. Quinolone drug resistance gene mediated by tetrandrine on drug-resistant escherichia coli plasmidaac(6’)-Ib-crInfluence of expression amount
Quinolone drug-resistant escherichia coli with the concentration of 1/4 multiplied by MIC before and after the tetrandrine is cultured is used as a research object, and the quinolone drug-resistant genes of the tetrandrine drug-resistant escherichia coli before and after the tetrandrine is cultured are comparedaac(6’)-Ib-crThe amount of mRNA expressed varies.
Escherichia coli housekeeping genegapAAs an internal reference gene, a synthetic primer of Shanghai Bioengineering technology, Inc. was designed and entrusted:gapA-F：5’-cagaacatcatcccgtcctctac-3’，gapA-r: 5'-taccagtcagtttgccattcagtt-3', according to genebankaac(6’)-Ib-crDesign of the Gene sequence and Synthesis of primers：aac(6’)-Ib-cr-F：5’-gttaggcatcacaaagtacagcat-3’，aac(6’)-Ib-cr-R：5’-catagagcatcgcaaggtcat-3’。
And (3) bacterial treatment:
after the tested Escherichia coli is cultured for 8-12 h, the Escherichia coli is inoculated into LB broth and cultured until the logarithmic phase of growth (OD)600= 0.7-0.8). The drug-resistant strain before tetrandrine culture is used as a control group, and the strain after tetrandrine culture is used as a test group.
And (3) gene expression quantity determination:
a RNA extraction and detection
(1) And standing the cracked sample at room temperature for 5-10 min.
(2) 0.2 mL of chloroform was added and shaken vigorously for 30 sec. Standing at room temperature for 3 min. Centrifugation at 12,000 rpm for 10min at 4 ℃.
(3) And (4) sucking the supernatant into a clean centrifugal tube, adding 1/2 times of absolute ethyl alcohol, and fully and uniformly mixing.
(5) Putting the adsorption column into the collecting tube, adding the solution and suspended substance into the adsorption column, and standing for 2 min. Centrifuging at 12,000 rpm for 3min, and finally, pouring waste liquid in the collecting pipe.
(6) Repeat step 5 once.
(7) The adsorption column was returned to the collection tube and centrifuged at 10000 rpm for 2 min.
(8) Putting the adsorption column into a 1.5 mL centrifuge tube, and adding 30 mu L DEPC-treated dd H in the center of the membrane2O, standing for 5min, centrifuging at 12,000 rpm for 2min, and storing the obtained RNA solution at-70 ℃.
(9) The RNA extraction results were examined (1.5% agarose, 1 XTAE electrophoresis buffer, visualization under UV transmission and photography).
b, reverse transcription: first Strand cDNA Synthesis (RNA reverse transcription 800 ng)
(1) The following reagents were added to ice-bath nucleo-free PCR tubes:
total RNA 5.0µL
Random Primer p(dN)6（100pmol） 1.0µL
dNTP Mix（0.5 mM final concentration)） 1.0 µL
rnase-free ddH2O to volume of 14.5 mu L
(2) Mixing, centrifuging for 3-5s, bathing the mixture at 65 deg.C for 5min, ice-cooling for 2min, and centrifuging for 3-5 s.
(3) The tube was ice-cooled and the following reagents were added:
4.0 μl 5*RT Buffer
0.5 μl Thermo Scientific RiboLock RNase Inhibitor（20U）
1.0 μl RevertAid Premium Reverse Transcriptase（200U）
(4) gently mixing and centrifuging for 3-5 seconds
(5) Reverse transcription reaction was performed on a PCR instrument under the following conditions
Incubation at ① 25 deg.C for 10 min;
② cDNA synthesis, 50 ℃ for 30 min;
③ terminating the reaction, at 85 deg.C for 5min, treating, and standing on ice;
(6) the above solution was stored at-20 ℃.
c fluorescent quantitative PCR detection
c.1 diluting the cDNA sample by 10 times and using the cDNA sample as a template to carry out machine detection, wherein the PCR reaction comprises the following steps:
c.2 prepare reaction mixtures as shown in Table 3.
TABLE 3 fluorescent quantitative PCR reaction System
| Reagent | Concentration of | Dosage (mu L) |
| SybrGreen qPCR Master Mix | | 10 |
| Primer F (10uM) | 10µM | 0.4 |
| Primer R (10uM) | 10µM | 0.4 |
| ddH2O | —— | 7.2 |
| cDNA | —— | 2 |
| Total | —— | 20 |
c.3 PCR cycling conditions: 95 ℃ for 3min, 95 ℃ for 3s, 60 ℃ for 30s, for a total of 45 cycles.
c.4 operation of the instrument: after the above steps were completed, the 96-well plate to which the sample was added was placed in an ABI Stebone plus type fluorescent quantitative PCR instrument for reaction.
By using 2-△△CtThe method performs data analysis, and the method controls the Escherichia coli 12-2aac(6’)-Ib-crWhen the gene expression level was set to 1.00, as shown in Table 4, the expression levels of Escherichia coli 12-2 and 16-1 in the test groups were determinedaac(6’)-Ib-crThe gene expression level is obviously reduced, which shows that the tetrandrine can obviously reduce the quinolone drug resistance gene mediated by drug-resistant escherichia coli plasmidaac(6’)- Ib-crExpression of (2).
TABLE 4 expression levels of drug-resistant E.coli gene aac (6') -Ib-cr before and after tetrandrine treatment
| Bacterial strains | Control group | Test group |
| 12-2 | 1±0.06 | 0.58±0.04 |
| 16-1 | 1.14±0.11 | 0.74±0.09 |
Finally, it is noted that the above-mentioned embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Sequence listing
<110> Chongqing Boolean animal pharmaceuticals Co., Ltd
Application of tetrandrine in preparation of escherichia coli drug-resistant inhibitor
<141>2020-03-12
<160>4
<170>SIPOSequenceListing 1.0
<210>1
<211>23
<212>DNA
<213> E.coli Artificial sequence (Escherichia coli)
<400>1
cagaacatca tcccgtcctc tac 23
<210>2
<211>24
<212>DNA
<213> E.coli Artificial sequence (Escherichia coli)
<400>2
taccagtcag tttgccattc agtt 24
<210>3
<211>24
<212>DNA
<213> E.coli Artificial sequence (Escherichia coli)
<400>3
gttaggcatc acaaagtaca gcat 24
<210>4
<211>21
<212>DNA
<213> E.coli Artificial sequence (Escherichia coli)
<400>4
catagagcat cgcaaggtca t 21
Claims (3)
1. Use of tetrandrine in preparation of Escherichia coli (E. coli)Escherichia coli) Application in drug resistance inhibitor.
2. The method of claim 1, wherein the Escherichia coli (E.coli) (E.coli) ()Escherichia coli) Is a strain of fluoroquinolone resistant drugs.
3. The method as claimed in claim 2, wherein the fluoroquinolone drug is ciprofloxacin or enrofloxacin.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113384580A (en) * | 2021-06-29 | 2021-09-14 | 中国农业大学 | New application of alkaloid in enhancing antibacterial effect of quinolone antibiotics |
| CN116889591A (en) * | 2023-06-26 | 2023-10-17 | 河南农业大学 | Application of coptis chinensis decoction in improving sensitivity of drug-resistant escherichia coli to ceftiofur |
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