Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth
Technical field
The present invention relates to effective component of chinese medicine vanillic acids as the research and development of the inhibitor of staphylococcus aureus and to answer
With, and in particular to vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth.
Background technique
Staphylococcus aureus (Staphylococcus aureus) is the principal causative for causing human infectious disease
Bacterium can cause many severe infections, can also cause pneumonia, pseudomembranous enteritis, pericarditis etc..Antibiotic is widely used, excessively
Using bacterial drug resistance is continuously increased, cause bacterial drug resistance in global constantly diffusion, " superbacteria " continuously emerges, become
The focus of global concern.The generation of multi-drug resistant bacteria brings huge challenge to clinical treatment, for example, invalid treatment not only promotees
Postpone the state of an illness, and consumes social resources, aggravates national public finance burden.
On the problem of enhancing in face of bacterial drug resistance, Chinese herbal medicine shows advantageous advantage, for example, having poison secondary
Act on the advantage and characteristic that small, medicine source is extensive, cheap.Thus, safely and effectively it is efficiently low to become people's searching for Chinese herbal medicine
The new sources of the bacterial inhibitor of poison.
Vanillic acid as one of effective components of plants such as vanilla beans, vanilla pod and Radix picrorrhizae, both at home and abroad to its
Antibacterial anti-inflammatory, it is anti-oxidant, inhibit tyrosinase activity, allelopathy, adjust nerve and procoagulant activity in terms of have it is certain
Research, but report is less in terms of vanillic acid inhibits bacterial growth.
(Huang Yuqian, Yang Jingfeng, Liang Chunhao, old Shen put down one, Liu Xinyu to document, and honest and just clod of earth is farsighted, Yao Yuchen, Zhang Yu, Han Xiao
Vanillic acid is to Germinating Peanut Seeds, growth of seedling and the influence of rhizosphere microflora [J] Scientia Agricultura Sinica, and 2018,51
(09): 1735-1745. the vanilla acid solution for) reporting various concentration can be such that the quantity of peanut rhizosphere bacteria and actinomyces drops
It is low, inhibit the growth and breeding of bacterium and actinomyces in rhizosphere soil, and low rush high the phenomenon that pressing down is presented in the influence to soil fungi,
The growth of fungi i.e. in the vanilla acid solution promotion peanut rhizosphere soil of low concentration, and the vanilla acid solution of high concentration is then to fungi
Growth has certain inhibiting effect.About using vanillic acid as the report for inhibiting multidrug resistant staphylococcus aureus active constituent
Road is not yet found.
Summary of the invention
The present invention is directed to the clinical drug-resistant problem of above-mentioned elaboration, starts with from existing resources of medicinal plant library, excavates potential
Drug resistance bacteria inhibitor, and it is an object of the present invention to provide vanillic acid inhibit multidrug resistant staphylococcus aureus growth in application, be
It develops novel antibiotic substitute and the multidrug resistant predicament offer practical basis of resistant Staphylococcus aureus is provided.
To achieve the goals above, the technical solution adopted by the present invention are as follows:
Vanillic acid is inhibiting the application in multidrug resistant staphylococcus aureus growth.
Preferably, the resistant Staphylococcus aureus is the resistance to Linezolid of source of people, trimethoprim, gentamicin, cyclopropyl
Sha Xing, penicillin, cephazoline, clindamycin, vancomycin, oxacillin, in Piperacillin Multiple Classes of Antibiotics golden yellow
Staphylococcus.
Preferably, the vanillic acid minimum bactericidal concentration is 2.4mg/mL, minimal inhibitory concentration 0.3mg/mL.
The beneficial effects of the present invention are embodied in:
Research the present invention is based on vanillic acid to the effect of source of people multidrug resistant staphylococcus aureus, is pressed down using vanillic acid
The growth of multidrug resistant staphylococcus aureus processed is the research and development and application of multidrug resistant staphylococcus aureus inhibitor
New thinking is provided, is with a wide range of applications in fields such as food, drugs.
It is husky to antibiotic-resistant Linezolid, trimethoprim, gentamicin, cyclopropyl that the present invention has further clarified vanillic acid
Star, penicillin, cephazoline, clindamycin, vancomycin, oxacillin, the source of people staphylococcus aureus of Piperacillin are resistance to
The inhibiting effect of pharmacological property is effectively relieved or solves the problems, such as the drug resistant infection of multidrug resistant staphylococcus aureus, reduces case fatality rate.
Specific embodiment
The present invention is described in further details below with reference to embodiment.It is described that the examples are only for explaining the invention, and
Non- limiting the scope of the invention.
1, the drug sensitive experiment of source of people staphylococcus aureus
The present invention is bacterium germination with 10 plants of source of people staphylococcus aureuses (bacterial strain sample is derived from disease prevention and control center)
Strain, select Linezolid, trimethoprim, gentamicin, Ciprofloxacin, penicillin, cephazoline, clindamycin, vancomycin,
The drug susceptability test paper piece progress drug sensitive test of 10 kinds of oxacillin, Piperacillin common antibiotics.
The pure bacterium colony uniform dissolution of picking culture 18~for 24 hours adjusts its turbidity and 0.5 in 2~5mL sterile saline
Maxwell opacity tube equal turbidity.50~200 μ L bacterium solutions of sterile absorption, even spread plate place 3~5min at room temperature.With sterile tweezer
Drug sensitive test paper (diameter 6mm) is tightly attached to planar surface as required by son, and every kind susceptibility piece three parallel.By inoculated plate
Be placed in 36~37 DEG C be incubated for 16~for 24 hours.Antibacterial circle diameter is measured with the vernier caliper of 0.02mm precision, with the diameter of inhibition zone
To judge that the sensibility of drug, antibacterial result are marked according to U.S. clinical trial room national standardization administration committee (CLSl2017)
Standard determines that criterion is shown in Table 1.Experimental result is shown in Table 2, faces the results show that 2# source of people staphylococcus aureus can be resistant to 8 kinds
Common antibiotic on bed, therefore as the research object of next step experiment.
Table 1. U.S. clinical trial room national standardization administration committee (CLSl2017) standard determination result
Antibacterial circle diameter result in the drug sensitive experiment of 2. source of people staphylococcus aureus of table
Note: the unit of antibacterial circle diameter is mm in table 2, and numerical value is three parallel average values;
2, inhibiting effect of the vanillic acid to multiple antibiotic resistant strain
In order to fully consider drug safety, the present invention is using vanillic acid single active ingredient as research object, with vancomycin
As positive control, the research of drug resistance inhibiting effect is carried out.The pure bacterium colony uniform dissolution of picking culture 18~for 24 hours is in 2~5mL
In LB liquid medium, its turbidity and 0.5 Maxwell opacity tube equal turbidity are adjusted, and measure its OD with microplate reader600Value.Use dimethyl
The vanillic acid that sulfoxide compound concentration is 30mg/mL is trained medical fluid, bacterium solution and LB liquid as medical fluid, using test tube doubling dilution
Support base and be added in 96 well culture plates and is incubated overnight, the medical fluid group of various concentration is three parallel, it is ensured that experimental data can
Reliability.
Using microplate reader measurement vanillic acid to the minimal inhibitory concentration (MIC) of multidrug resistant staphylococcus aureus.And it will
Culture solution under MIC concentration, which is placed in sterile LB liquid medium, to be continued to cultivate, using microplate reader measurement vanillic acid to multiple
The minimum bactericidal concentration (MBC) of resistant Staphylococcus aureus, experimental result is shown in Table 3.
The suppression result of 3. vanillic acid of table and vancomycin to source of people multidrug resistant staphylococcus aureus
As shown in Table 3, vanillic acid is mould to resistance to trimethoprim, gentamicin, Ciprofloxacin, penicillin, cephazoline, crin
Element, oxacillin, Piperacillin multidrug resistant staphylococcus aureus inhibiting effect it is preferable, MIC be 300 μ g/mL,
MBC is 2400 μ g/mL.
According to the above experimental result, the drug resistance feature of pathogenic bacteria of drug-resistant is solved in conjunction with Chinese herbal medicine, it can be by obtaining activity
Single-item ingredient vanillic acid plays inhibiting effect directly against clinical main multidrug resistant staphylococcus aureus, can effectively delay
Solution or the drug resistant infection for solving the problems, such as multidrug resistant staphylococcus aureus reduce case fatality rate, to inhibit source of people multidrug resistant gold
Staphylococcus aureus proposes new thinking, has important practice significance.