A multi-mechanism synergistic broad-spectrum antimicrobial peptide and its application

Abstract

The present invention discloses a multi-mechanism synergistic broad-spectrum antimicrobial peptide and its application, belonging to the field of biomedicine technology, and provides a multi-mechanism synergistic broad-spectrum antimicrobial peptide, wherein the amino acid sequence of the antimicrobial peptide is one of SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 or SEQ ID NO.6. The antimicrobial peptide of the present invention introduces a phenylboronic acid molecule at the N-terminus. The antimicrobial peptide contains arginine and lysine, and has a high density of positive charges that can bind to negatively charged bacteria. The antimicrobial peptide also contains a hydrophobic chain that can be inserted into the phospholipid bilayer to disrupt the cell membrane. The interaction between the phenylboronic acid structure and the bacterial surface polysaccharide changes the permeability of the bacterial cell membrane, causing the leakage of intracellular substances, thereby inhibiting the growth and reproduction of the bacteria.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a multi-mechanism synergistic broad-spectrum antimicrobial peptide and its application. Background Art

[0002] The widespread use of antibiotics has led to the emergence of bacterial resistance and even superbugs. However, antibiotic development is costly, and the development of new antibiotics lags far behind the emergence of new resistant bacteria. Furthermore, antibiotics may cause adverse reactions in the host. Peptides play a key role in regulating biological processes in living organisms and are of great significance to biology, medicine, and industry. Antimicrobial peptides (AMPs) are an important component of the innate immune defense mechanism of most organisms against pathogens. Compared with other antimicrobial drugs, they have advantages such as a broad antimicrobial spectrum, low drug resistance, low toxicity, rapid bactericidal ability, and good biocompatibility. Compared with traditional antibiotics, AMPs have a unique antimicrobial mechanism, typically killing bacteria by disrupting the integrity of the bacterial cell membrane rather than acting on the bacterial metabolic pathways. This mechanism makes it difficult for bacteria to develop drug resistance through simple genetic mutations, thus offering significant advantages in combating drug-resistant bacterial infections. In summary, antimicrobial peptides have significant advantages in antimicrobial spectrum, drug resistance, toxicity, thermal stability and biocompatibility, making them an ideal alternative to traditional antimicrobial drugs, especially with broad application prospects in dealing with drug-resistant bacterial infections. Summary of the Invention

[0003] To solve the above technical problems, the present invention proposes a multi-mechanism synergistic broad-spectrum antimicrobial peptide and its application. The antimicrobial peptide of the present invention introduces a phenylboronic acid molecule at the N-terminus. The presence of arginine and lysine in the antimicrobial peptide has a high density of positive charges and can bind to negatively charged bacteria. The antimicrobial peptide also contains a hydrophobic chain that can insert into the phospholipid bilayer to disrupt the cell membrane. The interaction between the phenylboronic acid structure and the bacterial surface polysaccharide changes the permeability of the bacterial cell membrane, causing the leakage of intracellular substances, thereby inhibiting the growth and reproduction of bacteria. It can effectively inhibit Gram-negative and Gram-positive bacteria, and exert a synergistic antibacterial effect.

[0004] To achieve the above objectives, the present invention provides a multi-mechanism synergistic broad-spectrum antimicrobial peptide, the amino acid sequence of which is one of SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 or SEQ ID NO.6.

[0005] Preferably, the multiple mechanisms synergize to introduce phenylboronic acid into the N-terminus of the broad-spectrum antimicrobial peptide.

[0006] The present invention also provides the use of the multi-mechanism synergistic broad-spectrum antimicrobial peptide in the preparation of antimicrobial products.

[0007] Preferably, the antibacterial product is a product against Gram-negative bacteria and / or Gram-positive bacteria.

[0008] Preferably, the antibacterial product is a product against Escherichia coli and / or Staphylococcus aureus.

[0009] The present invention also provides a multi-mechanism synergistic broad-spectrum antimicrobial peptide solution, which is prepared by dissolving the multi-mechanism synergistic broad-spectrum antimicrobial peptide in ultrapure water; the amino acid sequence of the multi-mechanism synergistic broad-spectrum antimicrobial peptide is one of SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 or SEQ ID NO.6.

[0010] Preferably, the concentration of the multi-mechanism synergistic broad-spectrum antimicrobial peptide solution is 0.96-7.8 μM.

[0011] The present invention also provides the use of the multi-mechanism synergistic broad-spectrum antimicrobial peptide solution in the preparation of antimicrobial products.

[0012] Preferably, the antibacterial product is a product against Gram-negative bacteria and / or Gram-positive bacteria.

[0013] Preferably, the antibacterial product is a product against Escherichia coli and / or Staphylococcus aureus.

[0014] Compared with the prior art, the present invention has the following advantages and technical effects:

[0015] The multi-mechanism synergistic broad-spectrum antimicrobial peptide described in the present invention is composed of 13 amino acids, including phenylalanine, glycine, proline, leucine, alanine, lysine, and arginine. The position and type of amino acids in each antimicrobial peptide vary, but a phenylboronic acid molecule is introduced at the N-terminus. The antimicrobial peptide described in the present invention has good water solubility and excellent antimicrobial properties. The antimicrobial peptide described in the present invention contains arginine and lysine, which are rich in positive charges. The high density of positive charges can bind to negatively charged bacteria. The positive charges can bind to and destroy the negatively charged bacterial cell membrane through electrostatic adsorption. It also contains hydrophobic amino acids and their boron ions. The hydrophobic chains can insert into the phospholipid bilayer to destroy the cell membrane. The interaction between the phenylboronic acid structure and the bacterial surface polysaccharides changes the permeability of the bacterial cell membrane, causing the leakage of intracellular substances, thereby inhibiting the growth and reproduction of bacteria, and can play a synergistic antimicrobial role.

[0016] The present invention demonstrates the minimum inhibitory concentrations (MICs) of the antimicrobial peptides against Gram-positive and Gram-negative bacteria, demonstrating their significant antimicrobial activity against both Gram-negative and Gram-positive bacteria, making them suitable as broad-spectrum antimicrobial peptides. Furthermore, the peptides described herein have a short polypeptide sequence, comprising only 13 amino acids, making them easy to produce and low in cost, thus facilitating their application and promotion, and potentially becoming novel antimicrobial drug candidates. The present invention investigates the antimicrobial activity of antimicrobial peptides against Escherichia coli and Staphylococcus aureus. Through synergistic antimicrobial effects through multiple mechanisms, in a plate count experiment, six antimicrobial peptides achieved a 100% reduction in the CFU of both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus at a concentration of 7.8 µM. One antimicrobial peptide exhibited a MIC of only 0.98 µM against both Escherichia coli and Staphylococcus aureus. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0018] Figure 1 is the structural formula of the multi-mechanism synergistic broad-spectrum antimicrobial peptide of the present invention, wherein a is an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.1, b is an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.2, c is an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.3, d is an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.4, e is an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.5, and f is an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.6;

[0019] Figure 2 The CFU reduction percentages of the antimicrobial peptide with the amino acid sequence shown in SEQ ID NO. 1 at different concentrations against Escherichia coli and Staphylococcus aureus were measured by plate count method, wherein a represents the CFU reduction percentage of Escherichia coli and b represents the CFU reduction percentage of Staphylococcus aureus.

[0020] Figure 3 The plate count method is used to measure the CFU reduction percentages of the antimicrobial peptide with the amino acid sequence shown in SEQ ID NO. 2 against Escherichia coli and Staphylococcus aureus at different concentrations, wherein a is the CFU reduction percentage of Escherichia coli and b is the CFU reduction percentage of Staphylococcus aureus;

[0021] Figure 4The plate count method is used to measure the CFU reduction percentages of the antimicrobial peptide with the amino acid sequence shown in SEQ ID NO. 3 against Escherichia coli and Staphylococcus aureus at different concentrations, wherein a is the CFU reduction percentage of Escherichia coli and b is the CFU reduction percentage of Staphylococcus aureus;

[0022] Figure 5 The plate count method is used to measure the CFU reduction percentages of the antimicrobial peptide with the amino acid sequence shown in SEQ ID NO. 4 at different concentrations against Escherichia coli and Staphylococcus aureus, wherein a is the CFU reduction percentage of Escherichia coli and b is the CFU reduction percentage of Staphylococcus aureus;

[0023] Figure 6 The CFU reduction percentages of the antimicrobial peptide with the amino acid sequence shown in SEQ ID NO. 5 at different concentrations against Escherichia coli and Staphylococcus aureus were measured by plate count method, wherein a represents the CFU reduction percentage of Escherichia coli and b represents the CFU reduction percentage of Staphylococcus aureus;

[0024] Figure 7 The plate count method is used to measure the CFU reduction percentages of the antimicrobial peptide with the amino acid sequence shown in SEQ ID NO. 6 against Escherichia coli and Staphylococcus aureus at different concentrations, wherein a is the CFU reduction percentage of Escherichia coli and b is the CFU reduction percentage of Staphylococcus aureus;

[0025] Figure 8 The MICs of the multi-mechanism synergistic broad-spectrum antimicrobial peptide of the present invention against Escherichia coli and Staphylococcus aureus, wherein BFFK4 represents an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.1, BK4FF represents an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.2, BFFR4 represents an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.3, BR4FF represents an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.4, BFFRKRK represents an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.5, and BRKRKFF represents an antimicrobial peptide with an amino acid sequence as shown in SEQ ID NO.6;

[0026] Figure 9The zeta potentials of the multi-mechanism synergistic broad-spectrum antimicrobial peptides of the present invention at different concentrations are shown, wherein a represents the antimicrobial peptide with an amino acid sequence such as SEQ ID NO.1 represented by B-FF-K4 and the antimicrobial peptide with an amino acid sequence such as SEQ ID NO.2 represented by B-K4-FF, b represents the antimicrobial peptide with an amino acid sequence such as SEQ ID NO.3 represented by B-FF-R4 and the antimicrobial peptide with an amino acid sequence such as SEQ ID NO.4 represented by B-R4-FF, and c represents the antimicrobial peptide with an amino acid sequence such as SEQ ID NO.5 represented by B-FF-RKRK and the antimicrobial peptide with an amino acid sequence such as SEQ ID NO.6 represented by B-RKRK-FF. DETAILED DESCRIPTION

[0027] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0028] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Each smaller range between any intermediate value within a stated value or stated range and any other stated value or intermediate value within the stated range is also encompassed by the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0029] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0030] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be exemplary only.

[0031] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0032] Sources of materials used in the present invention: Escherichia coli used in the present invention ( E. coli) and Staphylococcus aureus ( S. aureus ) was purchased from Beijing Biobo Biotechnology Co., Ltd., Escherichia coli ( E. coli ) is Escherichia coli bio-67405, Staphylococcus aureus ( S. aureus ) is Staphylococcus aureus bio-52471.

[0033] The liquid broth culture medium used in the present invention is formulated as follows: 10 g of LB broth powder is added to 400 mL of distilled water, stirred and dissolved, the pH value is adjusted to 7, and sterilized by high pressure at 121° C. for 20 min. After sterilization, the mixture is stored at room temperature for later use.

[0034] The solid broth medium used in the present invention is formulated as follows: 10 g of LB broth powder, 7 g of agar powder, 400 mL of distilled water, stirring until completely dissolved, adjusting the pH to 7, autoclaving at 121° C. for 20 min, and storing at room temperature for later use.

[0035] Example 1

[0036] The six antimicrobial peptides described in the present invention were synthesized by Shanghai Jiepeptide Biotechnology Co., Ltd. using the solid phase method, and all chemicals used were of analytical grade.

[0037] The amino acid sequences and structural formulas of the six antimicrobial peptides provided by the present invention are as follows: Figure 1 As shown, the red structure is rich in high-density positively charged amino acids: arginine (R) and lysine (K). The positively charged amino acids can bind to the negative charges on the phospholipid molecules in the cell membrane through electrostatic adsorption, thereby achieving the effect of destroying the cell membrane. In addition, the six antimicrobial peptides contain hydrophobic amino acids, which can be inserted into the bacterial cell membrane, thereby destroying the cell membrane and combining with the bactericidal effect of boron ions to achieve a synergistic bactericidal effect. The abbreviations and amino acid sequences of the six antimicrobial peptides are: BFFK4: B(OH)2-FFGPLGLAGKKKK-NH2 (SEQ ID NO.1) The specific structural formula is as follows Figure 1 As shown in a; BK4FF: B(OH)2-KKKKGPLGLAGFF-NH2 (SEQ ID NO.2) The specific structural formula is as follows Figure 1 As shown in b; BFFR4: B(OH)2-FFGPLGLAGRRRR-NH2 (SEQ ID NO.3) The specific structural formula is as follows Figure 1 As shown in c; BR4FF: B(OH)2-RRRRGPLGLAGFF-NH2 (SEQ ID NO.4) The specific structural formula is as follows Figure 1 As shown in d; BFFRKRK: B(OH)2-FFGPLGLAGRKRK-NH2 (SEQ ID NO.5) The specific structural formula is as follows Figure 1As shown in e; BRKRKFF: B(OH)2-RKRKGPLGLAGFF-NH2 (SEQ ID NO.6) The specific structural formula is as follows Figure 1 As shown in f.

[0038] Example 2

[0039] Preparation of antimicrobial peptide solution:

[0040] 5.74 mg BFFK4 or 5.74 mg BK4FF were weighed separately and dissolved in 2 mL ultrapure water, and the pH of the two antimicrobial peptides was adjusted to 7 with 0.1 M NaOH to prepare 2 mM BFFK4 polypeptide solution or 2 mM BK4FF polypeptide solution, and placed in a refrigerator at 4 ° C for storage; 6.19 mg BFFR4 or 6.19 mg BR4FF were weighed separately and dissolved in 2 mL ultrapure water, and the pH of the two antimicrobial peptides was adjusted to 7 with 0.1 M NaOH to prepare 2 mM BFFR4 polypeptide solution or 2 mM BR4FF polypeptide solution, and placed in a refrigerator at 4 ° C for storage; 5.96 mg BFFRKRK and 5.96 mg BRKRKFF were weighed separately and dissolved in 2 mL ultrapure water, and the pH of the two antimicrobial peptides was adjusted to 7 with 0.1 M NaOH to prepare 2 mM BFFRKRK polypeptide solution or 2 mM BRKRKFF polypeptide solution was placed in a 4°C refrigerator for later use.

[0041] Preparation of Escherichia coli suspension and Staphylococcus aureus suspension:

[0042] Take out Escherichia coli and Staphylococcus aureus, dilute them to appropriate multiples and then spread them on the plate. After 18 hours of growth on the plate, pick out the single colony that has grown appropriately on the agar plate, pick the single colony of Escherichia coli and Staphylococcus aureus into 20mL of liquid broth culture medium, culture them on a shaker at 37℃, 170rpm for 8 hours, and store them at 4℃ after culture. Take 1mL of the cultured Escherichia coli liquid and Staphylococcus aureus liquid respectively, dilute them at different multiples and spread them on the plate. After spreading the plates, check the number of colonies grown by the liquid diluted at different multiples, and reversely calculate the number of colonies contained in the original liquid.

[0043] The plate count method was used to measure the CFU reduction percentage of different concentrations of antimicrobial peptides against Gram-negative bacteria Escherichia coli:

[0044] The dilution method was used to test MBC. Six 2mM antimicrobial peptide solutions were diluted to 31.25µM, 7.81µM, 1.95µM, 0.98µM, 0.49µM, and 0.25µM in a centrifuge tube. Escherichia coli grown to the logarithmic phase was diluted to 1×10 6To determine the CFU / mL, an equal volume of E. coli suspension was added to a centrifuge tube containing antimicrobial peptide solutions of varying concentrations. After incubation at 37°C, 170 rpm, and 2 hours, a 100µL sample was removed and spread on a culture plate. The plate was then incubated at 37°C for 18 hours. An E. coli suspension without antimicrobial peptide was also added as a negative control. The percentage reduction in CFU of E. coli at different peptide concentrations can be determined by counting colonies on the agar plate.

[0045] The plate count method was used to measure the CFU reduction percentage of different concentrations of antimicrobial peptides against Gram-positive bacteria Staphylococcus aureus:

[0046] The Staphylococcus aureus grown to the logarithmic phase was diluted to 1×10 6 CFU / mL. To test the CFU / mL, six 2mM antimicrobial peptide solutions were diluted in centrifuge tubes to 7.81µM, 3.9µM, 1.95µM, 0.98µM, 0.49µM, and 0.25µM. Equal volumes of Staphylococcus aureus suspension were added to the centrifuge tubes containing the antimicrobial peptide solutions at different concentrations. After incubation on a shaker at 37°C, 170 rpm for 2 hours, 100µL of the sample was removed, plated on a culture plate, and incubated at 37°C for 18 hours. A S. aureus suspension without antimicrobial peptide was set up as a negative control. The percentage reduction in CFU of S. aureus at different concentrations of antimicrobial peptide was determined by counting colonies on the agar plate.

[0047] The test results are as follows Figure 2 Middle a, Figure 3 Middle a, Figure 4 Middle a, Figure 5 Middle a, Figure 6 A and Figure 7 As shown in Figure a, the six antimicrobial peptides can achieve a 100% reduction in the CFU of E. coli at a concentration of 7.8µM. Among them, when the concentration of BFFR4 is reduced to 0.98µM, the CFU reduction percentage of E. coli can also reach 100%. The test results are as follows Figure 2 Middle b, Figure 3 Middle b, Figure 4 Middle b, Figure 5 Middle b, Figure 6 Zhongb and Figure 7 As shown in middle b, when the concentration of the six antimicrobial peptides was 7.8µM, the CFU reduction percentage of Staphylococcus aureus could reach 100%. Among them, when the concentration of BFFR4 and BR4FF was reduced to 0.98µM, the CFU reduction percentage of Staphylococcus aureus could reach 100%.

[0048] like Figure 8As shown, among the six antimicrobial peptides of the present invention, the minimum inhibitory concentration of BFFR4 against Escherichia coli is 0.96µM, the minimum inhibitory concentration of BR4FF against Escherichia coli is 1.95µM, the minimum inhibitory concentration of BFFK4 against Escherichia coli is 1.95µM, the minimum inhibitory concentration of BK4FF against Escherichia coli is 7.8µM, the minimum inhibitory concentration of BFFRKRK against Escherichia coli is 1.95µM, and the minimum inhibitory concentration of BRKRKFF against Escherichia coli is 1.95µM; the six antimicrobial peptides of the present invention Among the antimicrobial peptides, the minimum inhibitory concentration of BFFR4 against Staphylococcus aureus was 0.96µM, the minimum inhibitory concentration of BR4FF against Staphylococcus aureus was 0.96µM, the minimum inhibitory concentration of BFFK4 against Staphylococcus aureus was 3.9µM, the minimum inhibitory concentration of BK4FF against Staphylococcus aureus was 7.8µM, the minimum inhibitory concentration of BFFRKRK against Staphylococcus aureus was 1.95µM, and the minimum inhibitory concentration of BRKRKFF against Staphylococcus aureus was 1.95µM.

[0049] Example 3

[0050] Determination of Zeta potential of peptide solutions with different concentrations:

[0051] Six 2mM antimicrobial peptide solutions were diluted to 1mM, 0.5mM, 0.25mM, 0.1mM, and 0.05mM, respectively, for testing using a DTS1060C transparent sample cell with an excitation wavelength of 633nm and a protein dispersion medium with a refractive index of 1.450. Experiments were conducted at 25°C with a minimum and maximum number of runs set to 10 and 100, respectively. Each antimicrobial peptide sample was tested in triplicate and the average was calculated. The antimicrobial peptide samples were equilibrated for 120 seconds before each measurement.

[0052] The results are as follows Figure 9 Middle a, Figure 9 Zhongb and Figure 9 As shown in Figure c, the potentials of the six antimicrobial peptides are all positive, indicating that the molecular surfaces of the six antimicrobial peptides are all positively charged; secondly, with the increase in concentration, the surface potential of the antimicrobial peptides also gradually increases; the positive charge on the surface of the antimicrobial peptides can electrostatically combine with the negative charge on the surface of the bacteria, thereby destroying the bacterial cell membrane and killing the bacteria.

[0053] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A multi-mechanism synergistic broad-spectrum antimicrobial peptide, characterized in that: The amino acid sequence of the multi-mechanism synergistic broad-spectrum antimicrobial peptide is one of SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 or SEQ ID NO.

6.

2. The multi-mechanism synergistic broad-spectrum antimicrobial peptide according to claim 1, characterized in that: The multiple mechanisms synergistically introduce phenylboronic acid into the N-terminus of the broad-spectrum antimicrobial peptide.

3. Use of the multi-mechanism synergistic broad-spectrum antimicrobial peptide according to claim 1 or claim 2 in the preparation of antimicrobial products, characterized in that: The antibacterial product is a product against Escherichia coli and / or Staphylococcus aureus.

4. A multi-mechanism synergistic broad-spectrum antimicrobial peptide solution, characterized in that: The multi-mechanism synergistic broad-spectrum antimicrobial peptide is prepared by dissolving it in ultrapure water; the amino acid sequence of the multi-mechanism synergistic broad-spectrum antimicrobial peptide is one of SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 or SEQ ID NO.

6.

5. The multi-mechanism synergistic broad-spectrum antimicrobial peptide solution according to claim 4, characterized in that: The concentration of the multi-mechanism synergistic broad-spectrum antimicrobial peptide solution is 0.96-7.8 μM.

6. Use of the multi-mechanism synergistic broad-spectrum antimicrobial peptide solution according to claim 4 or claim 5 in the preparation of antimicrobial products, characterized in that: The antibacterial product is a product against Escherichia coli and / or Staphylococcus aureus.

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