CN111808841A - Method for eliminating antibiotic resistance of drug-resistant escherichia coli - Google Patents
Method for eliminating antibiotic resistance of drug-resistant escherichia coli Download PDFInfo
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Abstract
The invention discloses a method for eliminating antibiotic resistance of drug-resistant escherichia coli, which comprises the following steps: mixing a photo-thermal material and a mixed solution of antibiotics with an antibacterial effect on drug-resistant escherichia coli with the drug-resistant escherichia coli to obtain a to-be-treated bacterial liquid, irradiating the to-be-treated bacterial liquid by adopting near-infrared laser, and controlling the power of the laser to keep the temperature of the to-be-treated bacterial liquid at 45-100 ℃. According to the invention, a mixed solution of a photo-thermal material and an antibiotic is mixed with drug-resistant escherichia coli, and then near-infrared laser irradiation is adopted, namely based on a photo-thermal auxiliary mechanism, the drug resistance of the drug-resistant escherichia coli to the antibiotic is eliminated by using heat generated by the photo-thermal material under the irradiation of the near-infrared laser, so that the problem that the treatment efficiency of the conventional common antibiotic to the drug-resistant escherichia coli is greatly weakened or even ineffective is effectively solved; meanwhile, the method is simple, low in equipment investment, low in resource consumption and low in implementation difficulty, and is suitable for industrial use.
Description
Technical Field
The invention belongs to the technical field of drug resistance of drug-resistant escherichia coli, and particularly relates to a method for eliminating drug resistance of drug-resistant escherichia coli to antibiotics.
Background
Escherichia coli is one of the normal flora abundantly present in the human and animal intestinal tracts and has become an important nosocomial infection pathogen in recent years. With the use of a large amount of antibiotics, particularly third-generation cephalosporins, the escherichia coli continuously develops the drug resistance mechanism under selective pressure, which causes increasingly serious drug resistance problems and brings great difficulty to clinical treatment. At present, the treatment efficiency of common antibiotics to drug-resistant escherichia coli is greatly weakened and even ineffective. Therefore, it is necessary to develop a method for eliminating the resistance of drug-resistant E.coli to antibiotics, i.e., a method capable of making "ineffective" antibiotics effective again.
Disclosure of Invention
In view of the above, the present invention provides a method for eliminating drug resistance of drug-resistant escherichia coli to antibiotics, which utilizes heat generated by a photothermal material under near-infrared laser irradiation to eliminate drug resistance of drug-resistant escherichia coli to antibiotics based on a photothermal-assisted mechanism, enhances antibacterial efficacy of antibiotics to drug-resistant escherichia coli, and effectively solves the problem that the treatment efficiency of the existing common antibiotics to drug-resistant escherichia coli is greatly reduced or even ineffective.
The invention adopts the technical scheme that a method for eliminating the drug resistance of drug-resistant escherichia coli to antibiotics comprises the following steps: mixing a photo-thermal material and a mixed solution of antibiotics with an antibacterial effect on drug-resistant escherichia coli with the drug-resistant escherichia coli to obtain a to-be-treated bacterial liquid, irradiating the to-be-treated bacterial liquid by adopting near-infrared laser, and controlling the power of the laser so that the temperature of the to-be-treated bacterial liquid is maintained at 45-100 ℃.
In specific implementation, the antibiotics having an antibacterial effect on the drug-resistant escherichia coli can comprise antibiotics having an antibacterial effect on the drug-resistant escherichia coli, antibiotics having a low-efficiency antibacterial effect on the drug-resistant escherichia coli, and antibiotics having an 'ineffective' antibacterial effect on the drug-resistant escherichia coli, namely, the antibacterial rate of the antibiotics on the drug-resistant escherichia coli can be lower, and even the antibacterial rate is as low as infinite and close to zero; the low efficiency is not limited by specific antibacterial rate, but is only a relative concept, and is applicable to the method of the present invention, and antibiotics with improved antibacterial property to drug-resistant escherichia coli after the method is applied are all applicable to the present invention.
Preferably, the irradiation time of the near-infrared laser is 10min or more.
Preferably, the temperature of the bacterial liquid to be treated is maintained at 45-55 ℃, and the irradiation time of the near-infrared light is 10-25 min.
Preferably, the wavelength of the near-infrared laser is 808 nm.
Preferably, the preparation process of the mixed solution of the photothermal material and the antibiotic having an antibacterial effect against drug-resistant escherichia coli is as follows: and uniformly dispersing the photo-thermal material into deionized water to obtain a photo-thermal material solution, and then adding the antibiotic having an antibacterial effect on drug-resistant escherichia coli into the photo-thermal material solution to obtain the mixed solution.
Preferably, the mass concentration of the photo-thermal material solution is 1-150 mg/mL.
Preferably, the concentration of the antibiotic having an antibacterial effect against drug-resistant escherichia coli in the mixed solution is above the minimum inhibitory concentration of 1/8.
Preferably, the photo-thermal material is at least one of two-dimensional nano materials of titanium carbide MXene, black phosphorus and graphene oxide.
Preferably, the antibiotic having an antibacterial effect against drug-resistant escherichia coli is any one of a β -lactam antibiotic, an aminoglycoside antibiotic, and a tetracycline antibiotic.
Preferably, the effective viable count of the drug-resistant escherichia coli is 1 x 107CFU/mL or less.
The invention has the beneficial effects that: according to the invention, a mixed solution of a photothermal material and an antibiotic having an antibacterial effect on drug-resistant escherichia coli is mixed with the drug-resistant escherichia coli, near-infrared laser irradiation is adopted, the power of laser is controlled, so that a to-be-treated bacterial liquid is maintained at a stable temperature, namely based on a photothermal auxiliary mechanism, the drug resistance of the drug-resistant escherichia coli to the antibiotic is eliminated by using heat generated by the photothermal material under the irradiation of the near-infrared laser, namely the antibacterial effect of the antibiotic on the drug-resistant escherichia coli is enhanced, and the problem that the treatment efficiency of the conventional common antibiotic to the drug-resistant escherichia coli is greatly weakened or even ineffective is effectively solved; meanwhile, the method is simple, low in equipment investment, low in resource consumption and low in implementation difficulty, and is suitable for industrial use.
Drawings
FIG. 1 is a graph showing data on the antibacterial ratio of samples treated according to examples 1 to 9 of the present invention and comparative examples 1 to 11;
FIG. 2 shows the antibiotic concentrations of 1/4MIC of the samples of examples 10 to 18 of the present invention and comparative examples 1 to 290A data graph of the antibacterial rate of the photo-thermal treatment and the photo-thermal treatment;
FIG. 3 shows the antibiotic concentrations of 1/8MIC of the samples of examples 10 to 18 and comparative examples 1 to 2 of the present invention90A data graph of the antibacterial rate of the photo-thermal treatment and the photo-thermal treatment;
FIG. 4 shows the antibiotic concentrations of 1/16MIC for the samples of comparative examples 1-2 and 12-20 of the present invention90Data graph of the antimicrobial rate of time-on-light and no-on-light
FIG. 5 is a graph showing data on the antibacterial ratio of the samples of examples 19 to 21 according to the present invention;
FIG. 6 is a graph showing the antibacterial ratio data of the samples of examples 22 to 24 and comparative examples 21 to 23 according to the present invention;
FIG. 7 is a graph showing data on the antibacterial ratio of samples of examples 25 to 27 of the present invention;
FIG. 8 is a graph showing data on the antibacterial ratio of samples of examples 28 to 30 according to the present invention;
FIG. 9 is a graph showing the data of the antibacterial ratio of the samples of examples 31 to 33 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The invention provides a method for eliminating antibiotic resistance of drug-resistant escherichia coli, which comprises the following steps: mixing a photo-thermal material and a mixed solution of antibiotics with an antibacterial effect on drug-resistant escherichia coli with the drug-resistant escherichia coli to obtain a to-be-treated bacterial liquid, irradiating the to-be-treated bacterial liquid by adopting near-infrared laser, and controlling the power of the laser so that the temperature of the to-be-treated bacterial liquid is maintained at 45-100 ℃.
The antibiotic has antibacterial effect on Escherichia coli, and can be used for treating Escherichia coli; however, when the antibiotic is used in a large amount, the escherichia coli continuously develops a drug resistance mechanism under selective pressure, the treatment efficiency of the common antibiotic to the drug-resistant escherichia coli is greatly reduced, even is ineffective, namely, the common antibiotic cannot effectively inactivate the drug-resistant escherichia coli under the condition that the antibiotic concentration is lower than the minimum inhibitory concentration.
The invention utilizes the heat generated by the photo-thermal material under the irradiation of near-infrared laser to weaken or even eliminate the drug resistance mechanism of the drug-resistant escherichia coli by photo-thermal assistance to the common antibiotics with low efficiency or even no effect on the drug-resistant escherichia coli, thereby eliminating the drug resistance of the drug-resistant escherichia coli to the antibiotics, namely enhancing the antibacterial effect of the antibiotics to the drug-resistant escherichia coli.
The antibiotics with the antibacterial effect on the drug-resistant escherichia coli can comprise antibiotics with the antibacterial effect on the drug-resistant escherichia coli, antibiotics with the low-efficiency antibacterial effect on the drug-resistant escherichia coli, and antibiotics with the 'invalid' antibacterial effect on the drug-resistant escherichia coli, namely the antibacterial rate of the antibiotics on the drug-resistant escherichia coli can be lower, and even the antibacterial rate is as low as infinite and close to zero; the low efficiency is not limited by specific antibacterial rate, but is only a relative concept, and is applicable to the method of the present invention, and antibiotics with improved antibacterial property to drug-resistant escherichia coli after the method is applied are all applicable to the present invention.
Coli has the following resistance mechanism, that is, escherichia coli resists the action of antibacterial drugs mainly by the following means: (1) the permeability of the cell wall is changed, so that the antibacterial drug can not enter the body of the escherichia coli; namely, the permeability of the drug-resistant escherichia coli cell wall is low, so that common antibiotics such as tetracycline antibiotics and the like are prevented from entering the body of the drug-resistant escherichia coli, and the antibiotics cannot play an antibacterial role; (2) produce inactivated enzyme to inactivate or structurally alter the antibacterial agent. The inactivated enzyme produced by drug-resistant escherichia coli mainly comprises two major types of hydrolase and inactivating enzyme, wherein the hydrolase can destroy the drug to make the drug ineffective, for example, beta-lactamase can hydrolyze a beta lactam ring in beta-lactam antibiotics, so that the beta lactam antibiotics are inactivated; inactivating enzymes can modify certain genes in the antibacterial drug molecule which are necessary for maintaining antibacterial activity, so that the affinity of the genes with ribosomes of acting targets is greatly reduced, thereby losing the effect of inhibiting the synthesis of bacterial proteins, such as inactivating enzymes which can make aminoglycoside antibiotics ineffective.
According to the invention, the near-infrared laser is adopted to irradiate the bacteria liquid to be treated, which is obtained by mixing the photo-thermal material, the antibiotic and the drug-resistant escherichia coli, and the heat generated by the photo-thermal material under the irradiation of the near-infrared laser is utilized to change the permeability of the cell wall of the drug-resistant escherichia coli, namely, the permeability of the cell membrane of the drug-resistant escherichia coli to the antibiotic is increased, and the activities of hydrolase and inactivating enzyme generated by the drug-resistant escherichia coli are reduced, namely, the drug-resistant mechanism of the drug-resistant escherichia coli is weakened or even eliminated, so that the high-efficiency bactericidal activity of the common antibiotic which is low-efficiency or even ineffective to the drug-resistant escherichia coli is activated.
The invention also considers the influence of different factors in the antibacterial effect of the antibiotic on the drug-resistant escherichia coli through photo-thermal auxiliary enhancement.
(one) examine the influence of both photothermal and antibiotic in the method of the present invention for enhancing the antibacterial efficacy of antibiotic against drug-resistant Escherichia coli.
Example 1
The embodiment provides a method for eliminating the antibiotic resistance of drug-resistant escherichia coli, which comprises the following steps:
uniformly dispersing two-dimensional nano material titanium carbide MXene into deionized water to obtain titanium carbide MXene solution with mass concentration of 100mg/mL, and then adding beta-lactam antibiotic, namely penicillin into the photo-thermal material solution to ensure that the concentration of the penicillin reaches the minimum value that the bacteriostatic effect exceeds 90 percentInhibitory Concentration (MIC)90) I.e. penicillin at a concentration of 1/2MIC90To obtain a mixed solution of titanium carbide MXene and penicillin;
adding 100 mu L of mixed solution of titanium carbide MXene and penicillin into 100 mu L of drug-resistant escherichia coli to obtain a bacterial liquid to be treated, then irradiating the bacterial liquid to be treated by adopting near-infrared laser with the wavelength of 808nm, and controlling the power of the laser to ensure that the temperature of the bacterial liquid to be treated is maintained at 50 ℃ and the irradiation is carried out for 20min, so that the antibacterial effect of the penicillin on the drug-resistant escherichia coli is enhanced; and the bacteria liquid irradiated by the near-infrared laser is the processed sample.
Wherein the effective viable count of the drug-resistant Escherichia coli is 1 × 106CFU/mL。
Example 2
The procedure of example 1 was followed except that the antibiotic used in this example was amoxicillin among the β -lactam antibiotics.
Example 3
The procedure of example 1 was followed except that the antibiotic used in this example was ceftriaxone, which is a β -lactam antibiotic.
Example 4
The method is basically the same as that of example 1, except that the antibiotic used in this example is gentamicin among aminoglycoside antibiotics.
Example 5
The method was substantially the same as in example 1, except that the antibiotic used in this example was kanamycin among aminoglycoside antibiotics.
Example 6
Basically the same procedure as in example 1 was followed, except that the antibiotic used in this example was streptomycin among aminoglycoside antibiotics.
Example 7
Basically the same procedure as in example 1 was followed, except that the antibiotic used in this example was tetracycline among tetracycline antibiotics.
Example 8
The method is substantially the same as that of example 1, except that the antibiotic used in this example is minocycline, which is a tetracycline antibiotic.
Example 9
The method of example 1 was substantially the same except that the antibiotic used in this example was aureomycin among tetracycline antibiotics.
Comparative example 1
The method is basically the same as the method of the embodiment 1, except that no antibiotic is added in the comparative example, and no near-infrared laser irradiation is adopted, namely 100 mu L of titanium carbide MXene solution with the mass concentration of 100mg/mL and 100 mu L of drug-resistant escherichia coli are mixed to obtain the bacterial liquid to be treated, namely the sample.
Comparative example 2
The method was substantially the same as in example 1, except that in this comparative example, no antibiotic was added, that is, 100. mu.L of a titanium carbide MXene solution having a mass concentration of 100mg/mL and 100. mu.L of a drug-resistant E.coli were mixed to obtain a bacterial solution to be treated, and then near-infrared laser irradiation was performed according to the method of example 1.
Comparative example 3
The bacterial suspension to be treated obtained in example 1.
Comparative example 4
The bacterial suspension to be treated obtained in example 2.
Comparative example 5
The bacterial suspension to be treated obtained in example 3.
Comparative example 6
The bacterial suspension to be treated obtained in example 4.
Comparative example 7
The bacterial suspension to be treated obtained in example 5.
Comparative example 8
The bacterial suspension to be treated obtained in example 6.
Comparative example 9
The bacterial suspension to be treated obtained in example 7.
Comparative example 10
The bacterial suspension to be treated obtained in example 8.
Comparative example 11
The bacterial suspension to be treated obtained in example 9.
In order to examine the influence of the photothermal process and the antibiotic in the method for enhancing the antibacterial efficacy of the antibiotic against drug-resistant escherichia coli according to the present invention, we performed antibacterial ratio detection by the plate coating method on the samples of examples 1 to 9 and comparative examples 1 to 11. Examples 1 to 9 and comparative examples 3 to 11 were used as test groups, wherein examples 1 to 9 were a photothermal group, i.e., a photothermal process was performed, and comparative examples 3 to 11 were a non-photothermal group, i.e., a photothermal process was not performed; meanwhile, the blank group was prepared by comparative example 1 and comparative example 2 in which only photothermal materials and drug-resistant E.coli were mixed, the non-photothermal group was prepared by comparative example 1 in which photothermal processing was not performed, and the photothermal group was prepared by comparative example 2 in which photothermal processing was performed.
Fig. 1 is a table showing the data of the antibacterial ratio of the samples treated in examples 1 to 9 and comparative examples 1 to 11, and table 1 is a table showing the data of the antibacterial ratio of the samples treated in examples 1 to 9 and comparative examples 1 to 11.
TABLE 1 data sheet of antibacterial rate of sample
As can be seen from fig. 1 and table 1, the antibacterial rates of the photo-thermal group and the non-photo-thermal group in the blank group are both very low, and the antibacterial rate of the blank test of the non-photo-thermal group is almost zero, which indicates that the anti-bacterial efficacy of antibiotics on the drug-resistant escherichia coli cannot be effectively enhanced by simply performing the photo-thermal treatment on the drug-resistant escherichia coli; the test group has the advantage that the antibacterial rate is obviously enhanced after photo-thermal irradiation, which indicates that the antibiotic and the drug-resistant escherichia coli are mixed and then are subjected to photo-thermal irradiation, so that the antibacterial effect of the antibiotic on the drug-resistant escherichia coli can be obviously enhanced.
And (II) investigating the influence of the concentration of the antibiotic in the method for enhancing the antibacterial efficacy of the antibiotic on the drug-resistant escherichia coli.
Example 10
Basically the same procedure as in example 1, except that the mixed solution of the photothermal material and the antibiotic in this example, titanium carbideThe concentration of the penicillin in the mixed solution of MXene and penicillin is 1/4MIC90And 1/8MIC90。
Example 11
Basically the same method as that of example 2, except that the concentration of amoxicillin in the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and amoxicillin, was 1/4MIC90And 1/8MIC90。
Example 12
Basically the same method as that of example 3, except that the concentration of ceftriaxone in the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and ceftriaxone, was 1/4MIC90And 1/8MIC90。
Example 13
Basically the same as the method in example 4, except that the concentration of gentamicin in the mixed solution of the photo-thermal material and the antibiotic in this example, i.e. the mixed solution of titanium carbide MXene and gentamicin, is 1/4MIC90And 1/8MIC90。
Example 14
Basically the same method as that of example 5, except that the concentration of kanamycin in the mixed solution of the photothermal material and the antibiotic in this example, that is, the mixed solution of titanium carbide MXene and kanamycin, was 1/4MIC, respectively90And 1/8MIC90。
Example 15
Basically the same method as that of example 6, except that the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and streptomycin, had a streptomycin concentration of 1/4MIC90And 1/8MIC90。
Example 16
Basically the same method as that of example 7, except that the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and tetracycline, had a concentration of tetracycline of 1/4MIC, respectively90And 1/8MIC90。
Example 17
Basically the same method as that of example 8, except that the concentration of minocycline in the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and minocycline, was 1/4MIC90And 1/8MIC90。
Example 18
Basically the same method as that of example 9, except that the concentrations of aureomycin in the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and aureomycin, were 1/4MIC90And 1/8MIC90。
Comparative example 12
Substantially the same procedure as in example 10, except that the mixed solution of the photothermal material and the antibiotic in this comparative example, that is, the mixed solution of titanium carbide MXene and penicillin, had a penicillin concentration of 1/16MIC90。
Comparative example 13
Substantially the same procedure as in example 11, except that the mixed solution of the photothermal material and the antibiotic in this comparative example, that is, the mixed solution of titanium carbide MXene and amoxicillin, had an amoxicillin concentration of 1/16MIC90。
Comparative example 14
Substantially the same procedure as in example 12, except that the mixed solution of the photothermal material and the antibiotic in this comparative example, i.e., the mixed solution of titanium carbide MXene and ceftriaxone, had a ceftriaxone concentration of 1/16MIC90。
Comparative example 15
Basically the same procedure as in example 13, except that the mixed solution of the photothermal material and the antibiotic in this example, i.e., the mixed solution of titanium carbide MXene and gentamicin, had a concentration of gentamicin of 1/16MIC90。
Comparative example 16
Substantially the same procedure as in example 14, except that the mixed solution of the photothermal material and the antibiotic in this comparative example, that is, the mixed solution of titanium carbide MXene and kanamycin had a kanamycin concentration of 1/16MIC90。
Comparative example 17
Substantially the same procedure as in example 15, except that the mixed solution of the photothermal material and the antibiotic in this example, the mixed solution of titanium carbide MXene and streptomycin, had a streptomycin concentration of 1/16MIC90。
Comparative example 18
Substantially the same procedure as in example 16, except that the mixed solution of the photothermal material and the antibiotic in this comparative example, that is, the mixed solution of titanium carbide MXene and tetracycline, had a tetracycline concentration of 1/16MIC90。
Comparative example 19
Substantially the same procedure as in example 17, except that the mixed solution of the photothermal material and the antibiotic in this example, the mixed solution of titanium carbide MXene and minocycline had a minocycline concentration of 1/16MIC90。
Comparative example 20
Substantially the same procedure as in example 18, except that the mixed solution of the photothermal material and the antibiotic in this comparative example, i.e., the mixed solution of titanium carbide MXene and aureomycin, had an aureomycin concentration of 1/16MIC90。
In order to examine the influence of the antibiotic concentration in the method for enhancing the antibiotic efficacy of drug-resistant Escherichia coli according to the present invention, the samples of examples 1 to 18 and comparative examples 12 to 20 were subjected to the antibacterial ratio test by the plate coating method.
Table 2 is a table of antibacterial ratio data of the samples treated in examples 1 to 18 and comparative examples 12 to 20.
TABLE 2 antibacterial Rate data Table of samples
As can be seen from Table 2, the concentrations of the various antibiotics were 1/2MIC90And 1/4MIC90The antibacterial rate is remarkably improved and the antibacterial effect is remarkably enhanced by photo-thermal treatment, wherein the aminoglycoside antibiotics and the tetracycline antibiotics have the concentration of 1/8MIC90The antibacterial effect is obviously enhanced by photo-thermal treatment, and the beta-interior isAmide antibiotics at the concentration of 1/8MIC90The antibacterial effect is less enhanced by photo-thermal treatment, and the antibiotic is 1/16MIC90The antibacterial rate is enhanced by photo-thermal treatment, but the enhancement effect is general, which indicates that the antibiotic concentration is 1/8MIC90The antibacterial effect of the light-heat treatment on the drug-resistant escherichia coli is obviously enhanced.
In addition, the present invention also performed experiments without photo-thermal treatment at antibiotic concentrations corresponding to examples 10 to 18 and comparative examples 1, 2, 12 to 20, and fig. 2, 3 and 4 respectively show antibiotic concentrations of 1/4MIC90、1/8MIC90And 1/16MIC90Table 3 is a table of data corresponding to fig. 2, fig. 3, fig. 4 for fig. 1, wherein the blank groups are comparative example 1 and comparative example 2.
TABLE 3 antibacterial Rate data Table of samples
And thirdly, investigating the influence of the power and the photo-thermal time of the near-infrared laser in the method for enhancing the antibacterial effect of the antibiotic on the drug-resistant escherichia coli.
In the invention, the power of the near-infrared laser is controlled to keep the bacteria liquid to be treated at a certain temperature, so that the temperature of the bacteria liquid to be treated is taken as an investigation index of the power of the near-infrared laser.
Example 19
Basically the same method as that of example 1, except that the temperature of the bacterial suspension to be treated was maintained at 45 ℃, 48 ℃ and 55 ℃ respectively when the bacterial suspension to be treated was irradiated with the near-infrared laser.
Example 20
Basically the same method as in example 6, except that the temperature of the bacterial suspension to be treated was maintained at 45 ℃, 48 ℃ and 55 ℃ when the bacterial suspension to be treated was irradiated with the near-infrared laser.
Example 21
Basically the same procedure as in example 7 was repeated, except that the temperature of the bacterial suspension to be treated was maintained at 45 ℃, 48 ℃ and 55 ℃ when the bacterial suspension to be treated was irradiated with the near-infrared laser.
Example 22
Basically the same as the method in example 1, except that when the bacterial liquid to be treated is irradiated with the near-infrared laser, the irradiation time is 10min, 15min and 25min, respectively.
Example 23
Basically the same as the method in example 6, except that when the bacterial liquid to be treated is irradiated with the near-infrared laser, the irradiation time is 10min, 15min and 25min, respectively.
Example 24
Basically the same as the method in example 7, except that when the bacterial liquid to be treated is irradiated with the near-infrared laser, the irradiation time is 10min, 15min and 25min, respectively.
Comparative example 21
Basically the same as the method in example 1, except that the irradiation time is 5min when the bacterial liquid to be treated is irradiated with the near-infrared laser.
Comparative example 22
Basically the same as the method in example 6, except that the irradiation time was 5min when the bacterial liquid to be treated was irradiated with the near-infrared laser.
Comparative example 23
Basically the same method as in example 7, except that when the bacterial liquid to be treated was irradiated with the near-infrared laser, the irradiation time was 5 min.
In order to examine the influence of the near-infrared laser power and the photothermal time in the method for enhancing the antibacterial efficacy of antibiotics on drug-resistant escherichia coli according to the present invention, we performed antibacterial ratio tests on the samples of example 1, example 6, example 7, example 19 to example 21, and comparative example 21 to comparative example 23 by the plate coating method.
Fig. 5 is data of antibacterial ratio of samples of examples 1, 6, 7, 19 to 21, and table 4 is a sample data table corresponding to fig. 5.
TABLE 4 antimicrobial data Table for samples
As can be seen from fig. 5 and table 4, when the temperature of the bacterial liquid to be treated reaches 45 ℃ by using near infrared light irradiation, the antibacterial rate of the antibiotic to the drug-resistant escherichia coli reaches 90.82%, and the antibacterial performance of the antibiotic to the drug-resistant escherichia coli is stable with the increase of the temperature.
Fig. 6 is antibacterial ratio data of samples of example 1, example 6, example 7, example 22 to example 24, and comparative example 21 to comparative example 23, and table 5 is a sample data table corresponding to fig. 6.
TABLE 5 antimicrobial data Table for samples
As can be seen from fig. 6 and table 5, when the photo-thermal time is 5min, the antibacterial rate of the antibiotic to the drug-resistant escherichia coli reaches 39.45%, the antibacterial effect is slightly improved, and when the photo-thermal time reaches 10min or more, the antibacterial effect of the antibiotic to the drug-resistant escherichia coli is significantly improved.
The influence of the power and the photo-thermal time of the near-infrared laser on the process of enhancing the antibacterial efficacy of antibiotics on drug-resistant escherichia coli is applicable to various antibiotics such as beta-lactam antibiotics, aminoglycoside antibiotics and tetracycline antibiotics, and the influence results are consistent, so the test process of taking penicillin, streptomycin and tetracycline as the antibiotics is only listed.
And (IV) investigating the influence of the type of the photothermal material and the solution concentration of the photothermal material in the method for enhancing the antibacterial effect of the antibiotic on the drug-resistant escherichia coli.
Example 25
Basically the same as the method in example 1, except that the photothermal material used in this example is black phosphorus, or graphene oxide, or a mixture of black scale and graphene oxide, or a mixture of two-dimensional nanomaterial titanium carbide MXene, black phosphorus, and graphene oxide.
Example 26
Basically the same method as that in example 6, except that the photothermal material used in this example is black phosphorus, or graphene oxide, or a mixture of black scale and graphene oxide, or a mixture of two-dimensional nanomaterial titanium carbide MXene, black phosphorus, and graphene oxide.
Example 27
Basically the same method as that in example 7, except that the photothermal material used in this example is black phosphorus, or graphene oxide, or a mixture of black scale and graphene oxide, or a mixture of two-dimensional nanomaterial titanium carbide MXene, black phosphorus, and graphene oxide.
Example 28
The method is substantially the same as that of example 1, except that the solution mass concentrations of the photothermal material in this example, that is, the mass concentrations of the titanium carbide MXene solution, were 1mg/mL, 10mg/mL, 50mg/mL, and 150mg/mL, respectively.
Example 29
The method was substantially the same as in example 6, except that the solution mass concentrations of the photothermal material in this example, that is, the mass concentrations of the titanium carbide MXene solution were 1mg/mL, 10mg/mL, 50mg/mL, and 150mg/mL, respectively.
Example 30
The method was substantially the same as in example 7, except that the solution mass concentrations of the photothermal material in this example, that is, the mass concentrations of the titanium carbide MXene solution were 1mg/mL, 10mg/mL, 50mg/mL, and 150mg/mL, respectively.
In order to examine the influence of the kind of the photothermal material and the solution concentration of the photothermal material in the method of enhancing the antibacterial efficacy of an antibiotic against drug-resistant escherichia coli according to the present invention, we performed the antibacterial ratio detection by the plate coating method on the samples of example 1, example 6, example 7, and example 25 to example 30.
Fig. 7 shows the antibacterial ratio data of the samples of examples 1, 6, 7 and 25 to 27, and table 6 shows a data table corresponding to fig. 7.
TABLE 6 antibacterial Rate data Table of samples
As can be seen from FIG. 7 and Table 6, the type of photothermal material has no effect in enhancing the antibacterial efficacy of antibiotics on drug-resistant Escherichia coli.
Fig. 8 is data of antibacterial ratios of samples of examples 1, 6, 7 and 28 to 30, and table 7 is a data table corresponding to fig. 8.
TABLE 7 antibacterial Rate data Table of samples
As can be seen from fig. 8 and table 7, the solution concentration of the photothermal material has no effect in enhancing the antibacterial efficacy of antibiotics against drug-resistant escherichia coli.
The influence of the type of the photo-thermal material and the solution concentration of the photo-thermal material in the process of enhancing the antibacterial efficacy of antibiotics on drug-resistant escherichia coli is applicable to various antibiotics such as beta-lactam antibiotics, aminoglycoside antibiotics and tetracycline antibiotics, and the influence results are consistent, so the test process of taking penicillin, streptomycete and tetracycline as the antibiotics is only listed.
And (V) investigating the influence of the effective viable count of the drug-resistant escherichia coli in the method for enhancing the antibacterial effect of the antibiotic on the drug-resistant escherichia coli.
Example 31
Basically the same procedure as in example 1, except that the effective viable count of the drug-resistant E.coli in this example was usedAre respectively 1 x 107CFU/mL、1*105CFU/mL、1*103CFU/mL、1*102CFU/mL。
Example 32
Basically the same method as example 6, except that the effective viable count of the drug-resistant E.coli in this example is 1 × 107CFU/mL、1*105CFU/mL、1*103CFU/mL、1*102CFU/mL。
Example 33
Basically the same method as example 7, except that the effective viable count of the drug-resistant E.coli in this example is 1X 107CFU/mL、1*105CFU/mL、1*103CFU/mL、1*102CFU/mL。
In order to examine the influence of the method for enhancing the antibacterial efficacy of antibiotics on drug-resistant escherichia coli according to the present invention, the antibacterial ratio of the samples of example 1, example 6, example 7, and example 31 to example 33 was measured by the plate coating method.
Fig. 9 is data of antibacterial ratios of samples of examples 1, 6, 7, 31 to 33, and table 8 is a table of correspondence data of fig. 9.
TABLE 8 data sheet for antimicrobial Rate of sample
As can be seen from FIG. 8 and Table 9, the effective viable count of the drug-resistant Escherichia coli has no effect in the process of enhancing the antibacterial efficacy of the antibiotic on the drug-resistant Escherichia coli.
The influence of the effective viable count of the drug-resistant escherichia coli on the process of enhancing the antibacterial efficacy of the antibiotic on the drug-resistant escherichia coli is applicable to various antibiotics such as beta-lactam antibiotics, aminoglycoside antibiotics and tetracycline antibiotics, and the influence results are consistent, so the test process of taking penicillin, streptomycin and tetracycline as the antibiotics is only listed.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (10)
1. A method for eliminating antibiotic resistance of drug-resistant Escherichia coli is characterized by comprising the following steps: mixing a photo-thermal material and a mixed solution of antibiotics with an antibacterial effect on drug-resistant escherichia coli with the drug-resistant escherichia coli to obtain a to-be-treated bacterial liquid, irradiating the to-be-treated bacterial liquid by adopting near-infrared laser, and controlling the power of the laser so that the temperature of the to-be-treated bacterial liquid is maintained at 45-100 ℃.
2. The method for eliminating the antibiotic resistance of drug-resistant escherichia coli according to claim 1, wherein the irradiation time of the near-infrared laser is 10min or more.
3. The method for eliminating the antibiotic resistance of the drug-resistant escherichia coli according to claim 2, wherein the temperature of the bacterial liquid to be treated is maintained at 45-55 ℃, and the irradiation time of the near-infrared light is 10-25 min.
4. The method for eliminating the antibiotic resistance of drug-resistant escherichia coli according to any one of claims 1 to 3, wherein the wavelength of the near-infrared laser is 808 nm.
5. The method for eliminating the antibiotic resistance of drug-resistant escherichia coli according to claim 1, wherein the preparation process of the mixed solution of the photothermal material and the antibiotic having an antibacterial effect on the drug-resistant escherichia coli comprises the following steps: and uniformly dispersing the photo-thermal material into deionized water to obtain a photo-thermal material solution, and then adding the antibiotic having an antibacterial effect on drug-resistant escherichia coli into the photo-thermal material solution to obtain the mixed solution.
6. The method for eliminating the antibiotic resistance of drug-resistant escherichia coli as claimed in claim 5, wherein the mass concentration of the photothermal material solution is 1-150 mg/mL.
7. The method for eliminating the antibiotic resistance of the drug-resistant escherichia coli according to claim 6, wherein the concentration of the antibiotic having an antibacterial effect on the drug-resistant escherichia coli in the mixed solution is above the minimum inhibitory concentration of 1/8.
8. The method for eliminating antibiotic resistance of drug-resistant escherichia coli according to any one of claims 5 to 7, wherein the photo-thermal material is at least one of two-dimensional nano materials of titanium carbide MXene, black phosphorus and graphene oxide.
9. The method for eliminating the antibiotic resistance of drug-resistant escherichia coli according to any one of claims 5 to 7, wherein the antibiotic having an antibacterial effect on the drug-resistant escherichia coli is any one of a beta-lactam antibiotic, an aminoglycoside antibiotic and a tetracycline antibiotic.
10. The method of claim 1, wherein the effective viable count of the drug-resistant escherichia coli is 1 x 107CFU/mL or less.
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