Application of MUC1 inhibitor in preparation of medicine for preventing and treating bacterial infection

Abstract

The invention relates to an application of an MUC1 inhibitor in preparation of a medicine for preventing and treating bacterial infection, in particular to an application of the MUC1 inhibitor in preparation of a preparation for improving the sensitivity of antibiotic treatment. By applying the MUC1 inhibitor, the effect of improving the sensitivity of the antibiotics for treating the bacterial infection can be achieved, the dosage of the antibiotics can be reduced by 50%, and a new strategy is provided for optimizing the dosage of the antibiotics for bacterial infection. In the application and the pharmaceutical composition provided by the invention, the MUC1 inhibitor has good cytocompatibility and no obvious cytotoxicity, and has a good application prospect in the field of biomedicine.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to the use of a MUC1 inhibitor in preparing a drug for preventing and / or treating bacterial infection. Background Art

[0002] Bacterial infection is a serious threat to human health and is one of the leading causes of death worldwide. As time goes by, bacteria continue to evolve and the misuse of antibiotics leads to rapid bacterial resistance. The common approach is to develop new antibacterial drugs. However, it takes at least 10-12 years for new antibacterial drugs to be developed and put into clinical use, while it only takes about 2 years for bacteria to develop resistance.

[0003] Therefore, there is an urgent need to develop new antimicrobial drugs and new anti-infection strategies. Summary of the invention

[0004] The purpose of the present invention is to provide the use of MUC1 inhibitors in the preparation of drugs for preventing or treating bacterial infections. MUC1 inhibitors can reduce the adhesion during bacteria-cell interaction. In the process of antibiotic prevention or treatment of bacterial infections, the addition of MUC1 inhibitors can significantly improve the sensitivity of antibiotic treatment, thereby reducing the dosage of antibiotics and reducing the generation of drug resistance.

[0005] To this end, in a first aspect, the present invention provides the use of a MUCl inhibitor for preparing a preparation for improving sensitivity to antibiotic treatment.

[0006] In some embodiments, the MUCl inhibitor is selected from GO-203TFA.

[0007] In some embodiments, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides.

[0008] In some embodiments, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin.

[0009] The second aspect of the present invention provides the use of a MUC1 inhibitor in the preparation of a drug for preventing and / or treating bacterial infection.

[0010] In some embodiments, the MUCl inhibitor is selected from GO-203TFA.

[0011] In some embodiments, the bacteria include at least one selected from the group consisting of Gram-negative bacteria and Gram-positive bacteria.

[0012] In some embodiments, the bacteria include at least one selected from the group consisting of Staphylococcus aureus, Escherichia coli, Streptococcus (eg, Pneumococcus), Mycobacterium tuberculosis, Klebsiella, Serratia, and Proteus.

[0013] In some embodiments, the MUCl inhibitor is present in the medicament at an effective dosage concentration.

[0014] In some embodiments, the medicament further comprises an antibiotic.

[0015] In some embodiments, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides.

[0016] In some embodiments, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin.

[0017] The third aspect of the present invention provides the use of a MUC1 inhibitor in combination with an antibiotic in the preparation of a medicament for preventing and / or treating bacterial infection.

[0018] In some embodiments, the MUCl inhibitor is selected from GO-203TFA.

[0019] In some embodiments, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides.

[0020] In some embodiments, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin.

[0021] In some embodiments, the bacteria include at least one selected from the group consisting of Gram-negative bacteria and Gram-positive bacteria.

[0022] In some embodiments, the bacteria include at least one selected from the group consisting of Staphylococcus aureus, Escherichia coli, Streptococcus (eg, Pneumococcus), Mycobacterium tuberculosis, Klebsiella, Serratia, and Proteus.

[0023] A fourth aspect of the present invention provides a pharmaceutical composition comprising a MUC1 inhibitor and an antibiotic.

[0024] In some embodiments, the MUCl inhibitor is selected from GO-203TFA.

[0025] In some embodiments, the concentration of the MUC1 inhibitor is 2.5 to 10 μM; for example, 2.5 μM, 3 μM, 3.5 μM, 4 μM, 4.5 μM, 5 μM, 5.5 μM, 6 μM, 6.5 μM, 7 μM, 7.5 μM, 8 μM, 8.5 μM, 9 μM, 9.5 μM, 10 μM, etc.

[0026] In some embodiments, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides.

[0027] In some embodiments, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin.

[0028] In some embodiments, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

[0029] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0030] The present invention provides related applications involving MUC1 inhibitors, including the use of MUC1 inhibitors in preparing preparations for improving the sensitivity of antibiotic treatment, the use of MUC1 inhibitors in preparing drugs for preventing and / or treating bacterial infections, and the use of MUC1 inhibitors in combination with antibiotics in preparing drugs for preventing and / or treating bacterial infections. The present invention also provides a pharmaceutical composition comprising MUC1 and antibiotics.

[0031] The present invention constructs a physical, mechanical and biological interaction experimental system between bacteria and cells, explores the regulation of MUC1 inhibitors on the adhesion of host cells and bacteria, verifies that MUC1 protein plays the role of adhesion target between host cells and bacteria, and provides a theoretical basis and principle explanation for the above-mentioned application and products of MUC1 inhibitors.

[0032] The present invention also verifies the effect of MUC1 inhibitors on reducing cell-bacteria adhesion and improving the sensitivity of antibiotics to treat bacterial infections through in vitro experiments. The use of MUC1 inhibitors can reduce the amount of antibiotics by 50%, providing a new strategy for optimizing the amount of antibiotics for bacterial infections.

[0033] In the above-mentioned application and pharmaceutical composition provided by the present invention, the MUC1 inhibitor has good cell compatibility and no obvious cytotoxicity, and has good application prospects in the biomedical field. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Various other advantages and benefits will become apparent to those of ordinary skill in the art by reading the detailed description of the preferred embodiments below. The accompanying drawings are only used for the purpose of illustrating the preferred embodiments and are not to be considered as limiting the present invention. In the accompanying drawings:

[0035] Figure 1 : Schematic diagram of the principle of MUC1 inhibitor regulating bacteria-host cell interaction, where (A) is a schematic diagram of the process of infection between bacteria and host cells through movement, adhesion, internalization and transmission, among which bacterial adhesion is the first key step of bacterial infection; (B) is a schematic diagram of the relationship between MUC1 inhibitor, cell-bacteria adhesion force and bacterial infection dose, and a representative fitting curve of adhesion force.

[0036] Figure 2 : Characterization results of MUC1 inhibitors for bacteria-host cell interactions, wherein (A) is a confocal imaging image of cells after co-incubation with GO-203TFA; (B) is a quantification result of MUC1 protein expression level in cells after co-incubation with GO-203TFA; (C) is a cell viability detection result after cells are treated with different concentrations of GO-203TFA; (D) is a confocal imaging image of cells infected with Staphylococcus aureus after cells are treated with GO-203TFA; (E) is a flow cytometer to detect the green fluorescence signal of Staphylococcus aureus in cells after cells are treated with GO-203TFA, and the total amount of bacteria adhering to infected cells is analyzed; (F) is a result of counting Staphylococcus aureus adhering to cells after cells are infected with Staphylococcus aureus after GO-203TFA treatment.

[0037] Figure 3 :The effect of MUC1 inhibitor on the adhesion between bacteria and host cells, wherein (A) is a schematic diagram of the measurement of single bacteria-cell adhesion based on fluid force microscopy; (B) a photo of the fluid force microscopy probe; (C) a comparison of the adhesion between cells not treated with MUC1 inhibitors and cells treated with MUC1 inhibitors and Staphylococcus aureus;

[0038] Figure 4 : Effects of MUC1 inhibitors on bacterial antibiotic sensitivity, where (A) is the survival rate of bacteria treated with different concentrations of GO-203TFA; (B) GO-203TFA-treated cells were infected with Staphylococcus aureus, and different concentrations of ciprofloxacin were added, and the colony counts of Staphylococcus aureus in the infected cells were taken; (C) is the statistical data of the colony count results in (B). DETAILED DESCRIPTION

[0039] The exemplary embodiments of the present disclosure will be described in more detail below with reference to the accompanying drawings. Although the exemplary embodiments of the present disclosure are shown in the accompanying drawings, it should be understood that the present disclosure can be implemented in various forms and should not be limited by the embodiments described herein. On the contrary, these embodiments are provided in order to enable a more thorough understanding of the present disclosure and to fully convey the scope of the present disclosure to those skilled in the art.

[0040] In some embodiments of the present invention, there is provided a use of a MUCl inhibitor for preparing a formulation for improving sensitivity to antibiotic treatment.

[0041] In some embodiments, a use of a MUC1 inhibitor in the preparation of a drug for preventing and / or treating bacterial infection is provided.

[0042] In some embodiments, there is provided a use of a MUCl inhibitor in combination with an antibiotic in the preparation of a medicament for preventing and / or treating bacterial infection.

[0043] In some embodiments, a pharmaceutical composition is provided that includes a MUCl inhibitor and an antibiotic.

[0044] In some embodiments, the MUC1 inhibitor is selected from GO-203TFA, which is an all-D amino acid peptide consisting of a poly-R transduction domain connected to a CQCRRKN ​​motif that binds to the MUC1 cytoplasmic tail and blocks MUC1 homodimerization; and can induce the production of reactive oxygen species and the loss of mitochondrial transmembrane potential. GO-203TFA is commercially available.

[0045] According to an embodiment of the present invention, the MUC1 inhibitor can significantly reduce the amount of bacterial adhesion and infection on cells during the interaction between cells and bacteria, thereby improving the antibiotic sensitivity of bacterial infection.

[0046] According to an embodiment of the present invention, MUC1 inhibitors can regulate the protein expression of MUC1 on the cell surface and significantly reduce the bacterial-cell adhesion, indicating that MUC1 mucin can serve as a new host-directed antibacterial target for blocking initial bacterial adhesion.

[0047] like Figure 1 As shown, Figure 1 It is a schematic diagram of the principle of regulating bacteria-host cell interaction by MUC1 inhibitors provided in an embodiment of the present invention. The present invention clarifies the relationship between MUC1 protein, bacteria-cell adhesion and bacterial infection by constructing an experimental system for physical, mechanical and biological interactions between bacteria and cells, thereby explaining the principle that MUC1 inhibitors can be used to improve the antibiotic sensitivity of bacterial infections.

[0048] In one embodiment of the present invention, a method for characterizing the regulation of cell-bacteria adhesion by a MUC1 inhibitor is as follows: IEC-6 cells are inoculated into a well plate, cultured for 12 hours to completely adhere to the wall, and a culture medium containing the MUC1 inhibitor GO-203TFA is added and cultured for 1 hour as an experimental group; before the experiment, a silicon nitride cantilever is selected for testing and calibration based on the size of the bacteria and the measurement object; during the experiment, a single live bacterium to be captured is searched in a liquid environment where bacteria and cells interact; then a fluid force microscope probe for capturing a single bacterium is brought close to the cell surface at a preset speed, stays for a preset time when a preset force is reached, and then returns to the probe to obtain adhesion force curve data between bacteria and cells; based on the obtained bacteria-cell adhesion force curve data, the adhesion force between bacteria and cells is calculated using an adhesion force calculation formula.

[0049] The inventive concept of the present invention includes, from the perspective of mechanical biology, discovering a new antibacterial target MUC1 protein that blocks the initial adhesion of bacteria by host-directed blocking, proposing the role of MUC1 inhibitors in improving the sensitivity of antibiotic treatment based on the force-biochemical changes mediated by the MUC1 protein, and screening out GO-203TFA.

[0050] According to an embodiment of the present invention, by using a MUC1 inhibitor, the dosage of antibiotics can be reduced by 50%, providing a new strategy for optimizing the dosage of antibiotics for bacterial infections.

[0051] According to an embodiment of the present invention, MUC1 inhibitors are used to improve the sensitivity of antibiotic treatment, have good cell compatibility, no obvious cytotoxicity, and inhibit bacterial infection by blocking the initial adhesion of bacteria in a host-oriented manner, which has potential application prospects in the biomedical field.

[0052] In the embodiments of the present invention, unless otherwise specified, the cell culture conditions are all 37° C. and 5% CO 2 .

[0053] Example 1

[0054] This example explores the regulation of bacterial adhesion and infection of cells by MUC1 inhibitors. Among them, this example uses rat intestinal crypt epithelial cells (IEC-6) as model host cells, which can form polarized monolayers and are often used to study the infection behavior of bacteria in host cells. In addition, this example selects Staphylococcus aureus (S.aureus ATCC29213), the most common pathogen in clinical practice, as a model pathogen, and pre-transfects Staphylococcus aureus with plasmid pSC19-GFP (erythromycin resistance) to express green fluorescent protein (GFP). The MUC1 inhibitor used in this example is GO-203TFA, purchased from MedChemExpress (MCE).

[0055] The specific steps are as follows:

[0056] First, IEC-6 cells were cultured at 1×10 6 The cells were inoculated into a 12-well plate at a concentration of 10 cells / well and cultured into a monolayer of epithelial cells. Subsequently, a medium containing GO-203TFA was added and incubated for 1 hour, wherein the concentration of GO-203TFA in the medium was set to the following gradient: control group: 0 (i.e., no GO-203TFA), experimental group: 2.5μM, 5μM, 7.5μM, 10μM; then washed twice with PBS, and then Staphylococcus aureus was added for infection for 2 hours to obtain the sample to be tested.

[0057] Detection and analysis:

[0058] (A) Laser confocal imaging and cell viability detection were performed on cells incubated with GO-203TFA for 1 hour.

[0059] Before imaging, DAPI was used to counterstain the nuclei and GO-203TFA was immunofluorescently stained. Figure 2 As shown in (A), Control represents the control group, 2.5 μM GO-203TFA represents the experimental group treated with 2.5 μM GO-203TFA, wherein blue indicates the cell nucleus and green indicates MUC1 protein. Figure 2(B) Quantification of MUC1 protein expression level in IEC-6 cells. Figure 2 (C) Cell viability test results of IEC-6 cells after treatment with different concentrations of GO-203TFA.

[0060] (II) Perform the following tests on the sample obtained after 2 hours of infection with Staphylococcus aureus:

[0061] 1. Analyze the total amount of bacteria adherent to infected cells using flow cytometry

[0062] The cells were digested with 0.25% (w / v) trypsin and then resuspended in 1 mL of PBS buffer containing 3% FBS. After filtering the cells through a 70 μm filter, the green fluorescence signal of intracellular bacteria was detected using a flow cytometer to analyze the total amount of bacteria adhering to infected cells. The results are shown in Figure 2 (E) as shown.

[0063] 2. Use colony counting method to detect the total amount of bacteria adhering to cells

[0064] After washing twice with PBS, all cells were lysed by supplementing the basal medium with 0.1% BSA and 0.1% Triton X-100 to release adherent and colonized bacteria. The lysed suspension was serially diluted and spread on agar plates, incubated overnight at 37°C and colony counted. Figure 2 (F)

[0065] 3. Use laser confocal fluorescence microscopy to detect the distribution of bacterial adhesion and colonization of host cells

[0066] Fix with 4% paraformaldehyde for 20 minutes and permeabilize the cells with 0.1% (v / v) Triton X-100 for 3 to 5 minutes. TM 555Ready Probes TM The reagents were used to label the F-actin cytoskeleton, the nuclei were counterstained with DAPI, and the bacteria stably expressed green fluorescent protein. The fluorescence distribution of bacteria adhering to host cells was analyzed by Nikon A1 software and Image J software. Figure 2 As shown in (D), red indicates F-actin; blue indicates cell nuclei; and green indicates Staphylococcus aureus.

[0067] Example 2

[0068] This example further verifies the mechanobiological mechanism of the MUC1 inhibitor regulating the cell-bacteria interaction force. This example mainly uses fluid force microscopy to analyze the adhesion force between a single bacterium and a cell, as follows:

[0069] First, IEC-6 cells were cultured at 1×10 6 The cells were inoculated into a 12-well plate at a concentration of 10 cells / well and cultured for 12 hours to completely adhere to the wall. Subsequently, a culture medium containing 5 μM MUC1 inhibitor GO-203TFA was added and cultured for 1 hour as the experimental group (a control group without GO-203TFA was also set up). Before the experiment, all culture media and buffers used were pre-filtered with a 0.22 μm filter. According to the size of the bacteria and the measurement object, a silicon nitride cantilever was selected for testing and calibration. During the experiment, a single live bacterium to be captured was searched in the liquid environment where bacteria and cells interact. A negative pressure was applied using a fluid force microscope pressure controller to cause the pinhole at the tip of the probe to absorb the bacteria, thereby obtaining a fluid force microscope probe that captures a single bacterium. Next, the fluid force microscope probe that captures a single bacterium is brought close to the cell surface at a preset speed, stays for a preset time when the preset force is reached, and then returns to the probe to obtain the adhesion force curve data between bacteria and cells. Based on the obtained bacteria-cell adhesion force curve data, the adhesion force between bacteria and cells is calculated using the adhesion force calculation formula, which is:

[0070] F=USK

[0071] Among them, U(v) is the voltage difference from when the probe is acted upon by adhesion force to when it returns to the initial state, S(m / v) is the probe sensitivity, and k(N / m) is the spring constant.

[0072] The statistical graph of the above adhesion calculation results is as follows Figure 3 As shown in (C), Control represents the control group and MUC1 represents the experimental group. It can be seen that the adhesion between cells and bacteria was significantly reduced by adding MUC1 inhibitor.

[0073] Example 3

[0074] This example evaluates the effect of MUC1 inhibitors on the sensitivity of bacterial antibiotic treatment, and the specific steps are as follows:

[0075] Provide a cell-bacteria interaction system: IEC-6 cells were cultured at 1×10 5 The cells were inoculated into LB broth medium in a 12-well plate at a concentration of 1.0×10 cells / well and cultured for 12 hours to allow complete attachment. Then, 1.0×10 6CFUs Staphylococcus aureus. In the experimental group, the following pretreatment was performed before the addition of antibiotics: 5 μM GO-203TFA was added to the cell-bacteria interaction system; in the control group, no pretreatment was performed. Then, different concentrations of the antibiotic ciprofloxacin were added to the cell-bacteria interaction system, and after incubation for 2 hours, the cells were washed twice with PBS, and then all cells were lysed by supplementing the basic culture medium containing 0.1% BSA and 0.1% TritonX-100 to release the adherent and colonized bacteria. The lysed suspension was serially diluted and spread on an agar plate, placed in a 37°C incubator for overnight culture, and photographed (the results are shown in Figure 4 (B), in which GO-203TFA represents the experimental group and Control represents the control group) and colony counts (statistical results are shown in Figure 4 (C) As shown in the figure, GO-203TFA represents the experimental group and Control represents the control group). Thus, the effect of the MUC1 inhibitor GO-203TFA on the sensitivity of bacterial antibiotic treatment was determined. It can be seen that by adding GO-203TFA, the sensitivity of bacterial infection to antibiotic treatment can be significantly improved.

[0076] In addition, this embodiment also provides Figure 4 (A) is used to illustrate that GO-203TFA itself has almost no killing effect on bacteria. The experimental method is to add gradient concentrations of GO-203TFA to 1.0×10 6 CFUs of Staphylococcus aureus were incubated in MH broth medium for 18 hours and the proportion of surviving bacteria was detected. Figure 4 (A) It can be seen that GO-203TFA has almost no killing effect on bacteria. The reason why it can improve the sensitivity of bacteria to antibiotic treatment is mainly due to reducing the adhesion of bacteria to cells.

[0077] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be based on the protection scope of the claims.

Claims

1. Use of MUC1 inhibitors for the preparation of preparations for improving the sensitivity of antibiotic treatment.

2. The use according to claim 1, characterized in that The MUC1 inhibitor is selected from GO-203TFA.

3. The use according to claim 1 or 2, characterized in that: The antibiotics include at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides; Preferably, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin.

4. Use of MUC1 inhibitors in the preparation of drugs for preventing and / or treating bacterial infections.

5. The use according to claim 4, characterized in that The MUC1 inhibitor is selected from GO-203TFA; Preferably, the MUCl inhibitor is present in the medicament at an effective dosage concentration.

6. The use according to claim 4 or 5, characterized in that The bacteria include at least one selected from the group consisting of: Gram-negative bacteria, Gram-positive bacteria; Preferably, the bacteria include at least one selected from the group consisting of Staphylococcus aureus, Escherichia coli, Streptococcus, Mycobacterium tuberculosis, Klebsiella, Serratia and Proteus; Preferably, the drug further comprises an antibiotic; Preferably, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides; Preferably, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin.

7. Use of a MUC1 inhibitor in combination with an antibiotic in the preparation of a drug for preventing and / or treating bacterial infection.

8. The use according to claim 7, characterized in that The MUC1 inhibitor is selected from GO-203TFA; Preferably, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides; Preferably, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin; Preferably, the bacteria include at least one selected from the group consisting of: Gram-negative bacteria, Gram-positive bacteria; Preferably, the bacteria include at least one selected from the group consisting of Staphylococcus aureus, Escherichia coli, Streptococcus, Mycobacterium tuberculosis, Klebsiella, Serratia and Proteus.

9. A pharmaceutical composition comprising a MUCl inhibitor and an antibiotic.

10. The pharmaceutical composition according to claim 9, characterized in that The MUC1 inhibitor is selected from GO-203TFA; Preferably, the concentration of the MUC1 inhibitor is 2.5 to 10 μM; Preferably, the antibiotic comprises at least one selected from the group consisting of cephalosporins, quinolones, fluoroquinolones, penicillins, beta-lactamase inhibitors, carbapenems, monobactams, macrolides, lincosamides, glycopeptides, rifampicins, oxazolidinones, tetracyclines, aminoglycosides, streptomyces and sulfonamides; Preferably, the antibiotic comprises a quinolone antibiotic, specifically comprising at least one selected from the group consisting of ciprofloxacin, enoxacin, gatifloxacin, grepafloxacin, levofloxacin, lomefloxacin, moxifloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, hydroxybenzoic acid, gemifloxacin or perfloxacin; Preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient.

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