CN110101838A - A method of improving the anti-Escherichia coli performance of histone - Google Patents
A method of improving the anti-Escherichia coli performance of histone Download PDFInfo
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- CN110101838A CN110101838A CN201910355139.0A CN201910355139A CN110101838A CN 110101838 A CN110101838 A CN 110101838A CN 201910355139 A CN201910355139 A CN 201910355139A CN 110101838 A CN110101838 A CN 110101838A
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Abstract
The invention discloses a kind of method for improving the anti-Escherichia coli performance of histone, this method is that DNA is formed to histone-DNA compound in conjunction with histone, wherein the DNA is the DNA being made of from the end 5' to the end 3' 8~15 duplicate AT base sequences.The method of the present invention is easy to operate, and the reaction time is short, low in cost, does not need excessive chemical modification and complicated large-scale instrument.Compared to histone, histone-DNA compound can be obtained significant bactericidal effect in the lower situation of histone concentration, and reduce the cytotoxicity of histone.
Description
Technical field
The invention belongs to antimicrobial technology fields, and in particular to a method of improve histone antibacterial activity.
Background technique
Escherichia coli (Escherichia coli) are pathogenic bacteria common in a kind of life, Chang Yinqi diarrhea and sepsis
Disease, it is a kind of both ends blunt circle, peritrichous, can move, nonspore-bearing Gram-negative brevibacterium, is distributed widely in nature
In, therefore food is very big by its pollution probability, easily causes food poisoning.For example, the spinach in the U.S. in 2006 is by Escherichia coli dirt
Dye, disease involve half of the U.S.；European " malicious cucumber " event in 2011 is also due to the sense of e. coli contamination vegetables initiation
Dye.Escherichia coli have caused repeatedly large-scale infection in the whole world, cause many people dead.In order to guarantee food safety,
Consumer can feel at ease to buy green, healthy food.A kind of novel Escherichia coli method for disinfection is studied, is had highly important
Meaning.
Escherichia coli method for disinfection common at present mainly takes antibiotic to be sterilized, due to largely using antibiotic,
Escherichia coli are made to produce drug resistance to many antibiotic, wherein 70% bacterium is at least resistant to a kind of medicine, and high concentration
Antibiotic to human body have certain harm.The antibiotic resistance problem of directed toward bacteria, novel antibiotic become research
Hot spot.Cationic polymer has the Antibacterial Mechanism different from Conventional antibiotic, is difficult bacterium as a kind of completely new antibacterial agent
Drug resistance is generated, and histone is one of the Typical Representative in cationic antibacterial peptide.
Histone (Histones) is chromosome basic structure albumen, due to being rich in basic amino acids arginine and lysine
In alkalinity, can combine closely with acid DNA.Histone includes five components, molecular mass 11-23ku, according to molecular weight
It is descending to be referred to as H, H3, H2A, H2B and H4.Contain a large amount of lysine and arginine in histone histone, wherein
Arginine is a kind of basic amino acid containing guanidine radicals, however, guanidine radicals acid dissociation constant with higher, and can be in water
Effectively dissolution, this makes them have stronger alkalinity, is more suitable for carrying out stable electrostatic with group negatively charged in phosphatide
Interaction.Since these guanidine radicals with positive charge largely exist, cause histone can be with electronegative bacterial cell membrane
Electrostatic interaction is generated, the result of this effect destroys cell wall or permeability of cell membranes, so that the growth of bacterium is inhibited,
Even it has been reported that they can penetrate plasma membrane.Histone is considered as that a kind of effective antibacterial peptide kills as a member in antibacterial peptide
Microbial inoculum, sterilization idiocratic were just found early in 1958, and the bactericidal activity of subsequent histone and its component is successively in software class, two
It is found in a variety of organisms such as class of dwelling.With the increase of histone concentration, antibacterial activity is higher, but cytotoxicity also with
Increase.Therefore, how to reduce the cytotoxicity of histone and to improve its antibacterial effect urgently to be resolved.
Summary of the invention
Making histone at low concentrations the object of the present invention is to provide one kind can reach preferable anti-Escherichia coli performance
Method.
For above-mentioned purpose, the method applied in the present invention is that DNA is formed to histone-DNA in conjunction with histone is compound
Object, wherein the DNA is the DNA being made of from the end 5' to the end 3' 8~15 duplicate AT base sequences.
In the method for above-mentioned raising histone antibacterial activity, preferably histone aqueous solution and aqueous dna are mixed, make institute
The concentration for obtaining DNA in mixed liquor is 0.001~0.03 μm of ol/L, the concentration of histone is 10~100 μ g/mL, at room temperature instead
It answers 1~3 hour, forms histone-DNA compound.
In the method for above-mentioned raising histone antibacterial activity, further preferably histone aqueous solution and aqueous dna are mixed
It closes, making 0.005~0.01 μm of ol/L of concentration of DNA, the concentration of histone in gained mixed liquor is 25~50 μ g/mL, in room
Temperature lower reaction 2 hours, form histone-DNA compound.
The DNA that above-mentioned DNA is preferably made of from the end 5' to the end 3' 8~10 duplicate AT base sequences.
Beneficial effects of the present invention are as follows:
DNA can fast and effeciently be formed histone-DNA compound by the present invention in conjunction with histone, easy to operate, instead
It is short between seasonable, it is low in cost, excessive chemical modification and complicated large-scale instrument are not needed, makes histone under lower concentration
There can be excellent anti-microbial property, reduce cytotoxicity.
Detailed description of the invention
Fig. 1 is the UV-visible absorption spectrum of histone in embodiment 1, DNA, histone-DNA compound.
Fig. 2 is the circular dichroism figure of histone in embodiment 1, DNA, histone-DNA compound.
Fig. 3 be histone in embodiment 1, DNA, histone-DNA compound circular dichroism partial enlarged view.
Sterilizing rate of the histone-DNA compound that Fig. 4 is histone and Examples 1 to 8 obtains to Escherichia coli.
Specific embodiment
The present invention is described in more detail with reference to the accompanying drawings and examples, but protection scope of the present invention is not limited only to
These embodiments.
Embodiment 1
The aqueous dna and 50 μ for being 5'-ATATATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
The mixing of 100 μ g/mL histone aqueous solution of L, reacts 2 hours at room temperature, forms histone-DNA compound.
By Fig. 1 ultraviolet spectrogram it is found that histone has an absorption peak in 275nm, this and calf chest reported in the literature
The peak position of gland histone UV absorption is consistent.DNA has apparent UV absorption at 265nm.With the purple of histone one pack system
Outer absorption compares, and the absorption peak of the compound formed after interaction occurs for DNA and histone in the peak position of histone
The conformation of upper enhanced strength and slightly blue shift, histone is changed.This demonstrates histones to finish really with DNA
Cooperation is used.By the circular dichroism of Fig. 2 as it can be seen that histone has an absorption peak in 210nm, and histone-DNA compound exists
Absorption intensity increases on this peak position, and slightly blue shift, illustrates that the molecular conformation of histone is changed, and hydrophobicity
Enhancing, it is consistent with its ultra-violet absorption spectrum.Since DNA absorption peak-to-peak value is smaller, so by this section of wavelength of 230nm to 300nm
Individually mapping.As shown in Figure 3, it can be seen that DNA has absorption at 245nm and 270nm, compared with the ultraviolet absorption peak of DNA
Compared with absorption of the histone-DNA compound at 275nm is declined.
Embodiment 2
The aqueous dna for being 5'-ATATATATATATATATATATATAT-3' by 50 μ L, 0.05 μm of ol/L base sequence
It mixes with 50 μ L, 50 μ g/mL histone aqueous solution, reacts 2 hours at room temperature, form histone-DNA compound.
Embodiment 3
The aqueous dna for being 5'-ATATATATATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
It mixes with 50 μ L, 50 μ g/mL histone aqueous solution, reacts 2 hours at room temperature, form histone-DNA compound.
Embodiment 4
The aqueous dna and 50 μ L 50 for being 5'-ATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
The mixing of μ g/mL histone aqueous solution, reacts 2 hours at room temperature, forms histone-DNA compound.
Embodiment 5
The aqueous dna and 50 μ for being 5'-ATATATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
The mixing of 50 μ g/mL histone aqueous solution of L, reacts 2 hours at room temperature, forms histone-DNA compound.
Embodiment 6
The DNA for being 5'-ATATATATATATATATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
Aqueous solution and the mixing of 50 μ L, 50 μ g/mL histone aqueous solution, react 2 hours at room temperature, form histone-DNA compound.
Embodiment 7
The aqueous dna and 50 μ for being 5'-ATATATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
The mixing of 200 μ g/mL histone aqueous solution of L, reacts 2 hours at room temperature, forms histone-DNA compound.
Embodiment 8
The aqueous dna and 50 μ for being 5'-ATATATATATATATATATAT-3' by 50 μ L, 0.01 μm of ol/L base sequence
The mixing of 25 μ g/mL histone aqueous solution of L, reacts 2 hours at room temperature, forms histone-DNA compound.
In order to prove beneficial effects of the present invention, inventor is compound to the histone-DNA in histone and Examples 1 to 8
The anti-microbial property of object has carried out contrast test, and specific test situation is as follows:
1, anti-Escherichia coli performance test
The anti-microbial property of antibacterial agent is usually characterized by minimum bactericidal concentration (MBC).MBC refers to that kill certain completely tested
The Cmin of antibacterial agent needed for bacterium, MBC value is smaller, and it is stronger to show that this material kills the ability that this kind of microorganism grows.
The measurement of MBC comprises the steps of:
(1) it weighs LB broth bouillon 25.0g to be added in 1L distilled water, boiling makes it after completely dissolution, adjusts pH to 7.2
~7.3,15g agar powder is added, after boiling dissolution, in 121 DEG C of high pressure sterilization 20min.After sterilizing, in being poured on aseptic operating platform
Plate is spare.Strain Escherichia coli cryopreservation tube is taken out from -80 DEG C of refrigerators, and after bacterium solution dissolution, bacterium solution is diluted with sterile water
It appropriate times, takes 100 μ L to be applied on plate, cultivates 18h at 37 DEG C.
(2) in super-clean bench, the LB liquid medium after taking out 20mL sterilizing is transferred in 100mL conical flask, with 10 μ L
Liquid-transfering gun draws a complete bacterium colony on above-mentioned plate, and pipette tips are squeezed into conical flask, shaking table (37 DEG C, 260r/min) are put into
It is incubated for 14h.
(3) it takes out and is incubated for the bacterium solution after 14h in shaking table, draw 5mL in 10mL centrifuge tube, centrifugation (6000r/min,
2min), supernatant is removed, 5mL physiological saline is added, (6000r/min, 2min) is centrifuged after mixing, is repeated twice, then is trained to washing away
It supports and 5mL physiological saline is added in the thallus of base, dilute 1 × 10 with the PBS buffer solution of pH=7.44100 μ L are taken after times, thereto
Histone-DNA compound (wherein Examples 1 to 5 after 100 μ L, 1.25 μ g/mL histone aqueous solution or 100 μ L dilution is added
Histone-DNA compound be diluted with water 80 times, the histone-DNA compound of embodiment 6 is diluted with water 40 times, embodiment 7
Histone-DNA compound be diluted with water 10 times, the histone-DNA compound of embodiment 8 is diluted with water 20 times), then use
The PBS buffer solution of pH=7.4 is settled to 1000 μ L, is put into (37 DEG C, 260r/min) incubation 5h of shaking table, 100 μ L is taken to be applied to plate
On, it is inverted culture 18h at 37 DEG C, observes bacterium colony growing state；And blank control experiment, parallel laboratory test 3 are done with PBS buffer solution
It is secondary.
The calculation method of sterilizing rate:
Sterilizing rate=(1- experimental group clump count/blank group clump count) × 100%
From fig. 4, it can be seen that in the case where histone concentration is 0.125 μ g/mL, compared to independent histone, this hair
Histone-DNA compound anti-microbial property obtained by bright Examples 1 to 8 significantly improves, wherein the group egg of embodiment 1,3,4,5,7
White-DNA compound anti-microbial property improves 1~3 times.
Claims (4)
1. a kind of method for improving the anti-Escherichia coli performance of histone, it is characterised in that: the method is by DNA and histone knot
Conjunction forms histone-DNA compound, wherein the DNA is from the end 5' to the end 3' by 8~15 duplicate AT base sequence structures
At DNA.
2. the method according to claim 1 for improving histone antibacterial activity, it is characterised in that: by histone aqueous solution and
Aqueous dna mixing, make in gained mixed liquor 0.001~0.03 μm of ol/L of concentration of DNA, the concentration of histone be 10~
100 μ g/mL react 1~3 hour at room temperature, form histone-DNA compound.
3. the method according to claim 2 for improving histone antibacterial activity, it is characterised in that: by histone aqueous solution and
Aqueous dna mixing, making 0.005~0.01 μm of ol/L of concentration of DNA, the concentration of histone in gained mixed liquor is 25~50
μ g/mL reacts 2 hours at room temperature, forms histone-DNA compound.
4. the method according to claim 3 for improving histone antibacterial activity, it is characterised in that: the DNA is from 5'
The DNA for holding the end 3' to be made of 8~10 duplicate AT base sequences.
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2019
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| WO2001051511A2 (en) * | 2000-01-13 | 2001-07-19 | Strathmann Ag & Co. | Recombinant production of human histone-1 subtypes and use thereof for therapeutic purposes |
| US20090117099A1 (en) * | 2007-11-06 | 2009-05-07 | Oklahoma Medical Research Foundation | Extracellular histones as biomarkers for prognosis and molecular targets for therapy |
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