TIR-STAND anti-bacteriophage and antiviral system and application thereof
By designing the TIR-STAND anti-phage system and utilizing a protein composition of TIR, NTPase and TPR domains, broad-spectrum resistance to multiple phages is achieved, addressing the shortcomings of the antiviral system in existing technologies and providing new directions for biotechnology and clinical applications.
Patent Information
- Application Number
- CN202510777087.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-11
- Publication Date
- 2025-09-19
AI Technical Summary
It is difficult for existing technologies to effectively solve the technical field of antiviral drugs. It is difficult for existing technologies to effectively utilize the anti-phage system of bacteria to provide broad-spectrum resistance to multiple phages, resulting in a lack of effective means for the anti-viral system of eukaryotes.
A TIR-STAND anti-phage and antiviral system was designed. It is a protein composition composed of TIR, NTPase and TPR domains. It can recognize and function phage signals through heterologous expression, providing broad-spectrum resistance to a variety of bacteria.
It has achieved effective resistance of host cells to multiple bacteriophages, expanded the understanding of anti-bacteriophage and antiviral systems, and provided new ideas for biotechnology development and clinical pathogen prevention and control.
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Figure CN120665201A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biotechnology, in particular to a TIR-STAND anti-phage and anti-virus system and applications thereof. Background Art
[0002] The innate immune system of eukaryotes senses viral molecules and activates downstream antiviral proteins to defend against viral infection. This system was long believed to have originated in prokaryotes. However, with the advancement of genomics, scholars have discovered that bacteria harbor numerous innate immune proteins that share homology with higher animals. Bacteria and their viruses have co-evolved for billions of years. This ancient and ongoing "arms race" has led bacteria to develop a vast arsenal of anti-phage weapons. Understanding the mechanisms of this diverse bacterial anti-phage defense system will provide insights into the antiviral mechanisms of the eukaryotic innate immune system. Summary of the Invention
[0003] The present invention provides a novel TIR-STAND anti-phage and anti-viral system and its applications. This system, through heterologous expression, utilizes a single protein to perform phage signal recognition and function, conferring broad-spectrum resistance to multiple phages in abortive infection on a variety of bacteria, thereby combating phage infection. Unlike some multi-system synergies and multi-protein interactions, this system expands existing understanding of anti-phage and anti-viral systems and provides new insights and applications for biotechnology development, clinical pathogen control, and anti-phage contamination in fermentation processes.
[0004] In the first aspect of the present invention, a protein composition is provided, which is composed of three structural domains: TIR, NTPase and TPR; the amino acid sequence of the TIR domain is shown as the sequence at positions 1-140 in SEQ ID NO.1 or the sequence at positions 1-140 in SEQ ID NO.2, the amino acid sequence of the NTPase domain is shown as the sequence at positions 141-590 in SEQ ID NO.1 or SEQ ID NO.2, and the amino acid sequence of the TPR domain is shown as the sequence at positions 591-824 in SEQ ID NO.1 or SEQ ID NO.2.
[0005] Furthermore, the amino acid sequence of the protein composition is shown as SEQ ID NO.1 or SEQ ID NO.2.
[0006] Our analysis revealed that the TIR (Toll / interleukin-1 receptor, Toll)-STAND (signal transduction ATPases with numerous associated domains) systems from Klebsiella pneumoniae strain CTKp47 NODE_7 and Escherichia coli strain possess characteristics of a defense system.
[0007] Based on these findings, the present invention designed a TIR-STAND anti-phage and anti-viral system, a protein composition comprising a TIR domain, an NTPase (nucleoside triphosphatases) domain, and a TPR (tetratricopeptide repeat) domain. TIR domain proteins play an important role in eukaryotic immune responses and include a variety of important signal transduction proteins, such as Toll-like receptors (TLRs), members of the IL-1 receptor family, RIG-I-like receptors (RLRs), and NOD-like receptors (NLRs).
[0008] The TIR-STAND protein composition provided by the present invention can recognize phage signals and function after activation, so that heterologous host cells can resist phage infection.
[0009] The second aspect of the present invention provides a nucleic acid molecule for encoding and expressing the above-mentioned protein composition.
[0010] Furthermore, the nucleotide sequence of the nucleic acid molecule is shown in any one of SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5, and SEQ ID NO.6.
[0011] The third aspect of the present invention provides a recombinant expression vector, which includes a gene fragment for encoding and expressing the above-mentioned protein composition, or includes the above-mentioned nucleic acid molecule.
[0012] A fourth aspect of the present invention provides a host cell for expressing the protein composition; or containing the nucleic acid molecule; or containing the recombinant expression vector.
[0013] The fifth aspect of the present invention provides the use of the above-mentioned protein composition, nucleic acid molecule, recombinant expression vector or host cell in the preparation of antiviral or anti-phage preparations.
[0014] In a sixth aspect, the present invention provides an anti-phage or anti-virus method that is not intended for disease diagnosis and treatment, wherein the nucleic acid molecule or recombinant expression vector used to express the above-mentioned protein composition is transferred into cells to be cultured to enhance the resistance of the cells to be cultured to bacteriophage or virus.
[0015] Furthermore, the cells to be cultured are Escherichia coli E. coli B, E. coli MG1655 or E. coli BL21 (DE3); and / or the bacteriophage is bacteriophage T1, JMPW2, T4, T5, T7, EEP, or λ.
[0016] Compared to existing technologies, the present invention is beneficial in that it discovers for the first time a novel TIR-STAND-based anti-phage immune defense system that protects the host against phage infection. This novel anti-phage or antiviral system, primarily found in bacteria, primarily comprises three domains: TIR, NTPase, and TPR. This invention expands existing understanding of the anti-phage immune system and provides new insights and applications for biotechnology development, clinical pathogen control, and anti-phage contamination in fermentation processes. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Figure 1 Schematic diagram of plasmid pWANGLab-AVS51, which contains the TIR-STAND gene cluster from Klebsiella pneumoniae strain CTKp47 NODE_7 based on plasmid pACYC184.
[0018] Figure 2 Schematic diagram of plasmid pWANGLab-AVS52, which contains the TIR-STAND gene cluster from Klebsiella pneumoniae strain CTKp47 NODE_7 based on plasmid pQE82L.
[0019] Figure 3 Schematic diagram of plasmid pWANGLab-AVS53, which is based on plasmid pACYC184 and contains the TIR-STAND gene cluster from Escherichia coli strain CVM N17EC0100 SAMN10221007-rid6731453.denovo.04.
[0020] Figure 4Schematic diagram of plasmid pWANGLab-AVS54, which contains the TIR-STAND gene cluster from Escherichia coli strain CVM N17EC0100 SAMN10221007-rid6731453.denovo.04 based on plasmid pQE82L.
[0021] Figure 5 The figure shows the resistance experiment results of E. coli B (Empty vector) and E. coli B (kpTIR-STAND, pWANGLab-AVS52) to bacteriophages T4, T5, and T7 after induction culture with 0.1 mM IPTG at 37°C.
[0022] Figure 6 This figure shows the resistance experiment results of E. coli MG1655 (Empty vector) and E. coli MG1655 (kpTIR-STAND, pWANGLab-AVS52) to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ after induction with 0.1 mM IPTG at 37°C.
[0023] Figure 7 The figure shows the resistance test results of E. coli BL21(DE3) (Empty vector) and E. coli BL21(DE3) (kpTIR-STAND, pWANGLab-AVS51) at 37°C without induction to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ.
[0024] Figure 8 The graph shows the resistance test results of E. coli MG1655 (Empty vector) and E. coli MG1655 (kpTIR-STAND, pWANGLab-AVS51) at 37°C without induction to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ.
[0025] Figure 9 The graph shows the resistance test results of E. coli MG1655 (Empty vector) and E. coli MG1655 (ecTIR-STAND, pWANGLab-AVS53) at 37°C without induction to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ.
[0026] Figure 10This figure shows the resistance experiment results of E. coli MG1655 (Empty vector) and E. coli MG1655 (ecTIR-STAND, pWANGLab-AVS54) to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ after induction with 0.1 mM IPTG at 37°C.
[0027] Figure 11 This figure shows the resistance experiment results of E. coli MG1655 (Empty vector), E. coli MG1655 (His-kpTIR-STAND, pQE82L-His-kpTIR-STAND), and E. coli MG1655 (kpTIR-STAND-Strep, pQE82L-kpTIR-STAND-Strep) to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ after culture at 37°C with 0.1 mM IPTG induction. DETAILED DESCRIPTION
[0028] The technical solutions of the present invention are described clearly and completely below. Obviously, the embodiments described are only some of the embodiments of the present invention, not all of them. All other embodiments obtained by persons of ordinary skill in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.
[0029] Example 1: Construction of a plasmid containing TIR-STAND
[0030] Through analysis, the present invention discovered TIR-STAND gene clusters in Klebsiella pneumoniae strain CTKp47NODE_7 and Escherichia coli strain CVM N17EC0100 SAMN10221007-rid6731453.denovo.04, constituting a bacterial immune defense system against bacteriophages. The amino acid sequences of the proteins encoded by the TIR-STAND gene cluster are shown in SEQ ID NO. 1 (WP_044784989.1) and SEQ ID NO. 2 (WP_059327187.1), respectively.
[0031] Based on the above findings, this example constructed a plasmid containing TIR-STAND by PCR and homologous recombination. The PCR amplification system and reaction procedures are shown in Tables 1 and 2 below.
[0032] Table 1
[0033]
[0034] Table 2
[0035] 1. Construction of pWANGLab-AVS51 containing kpTIR-STAND
[0036] (1) Plasmid pACYC184 was linearized to 4.2 kb after 30 rounds of PCR using NEB's Q5 High-Fidelity 2× Master Mix and primers 5'-gctttaatgcggtagtttatcac-3' (as shown in SEQ ID NO. 7) and 5'-ttatcgatgataagctgtcaaac-3' (as shown in SEQ ID NO. 8).
[0037] (2) Using plasmid pQE82L as a template and NEB's Q5 High-Fidelity 2× Master Mix with primers 5'-ataaactaccgcattaaagctcataaaaaatttatttgctttgtgag-3' (as shown in SEQ ID NO.9) and 5'-agttaatttctcctctttaatgaattc-3' (as shown in SEQ ID NO.10), a 0.12 kb fragment containing the T5-promoter was obtained after 30 rounds of PCR reaction.
[0038] (3) The nucleotide sequence shown in SEQ ID NO.3 (i.e., the nucleotide sequence before optimization of the protein composition containing the TIR domain expressed in Klebsiella pneumoniae strain CTKp47 NODE_7) was codon optimized. Using the codon-optimized pUC19-kpTIR-STAND (the optimized nucleotide sequence expressing the protein composition containing the TIR domain is shown in SEQ ID NO.4) as a template, NEB's Q5 High-Fidelity 2× Master Mix was used, and 5'-ttaaagaggagaaattaactATGATTAAGGCTTTCCTGAG-3' (as shown in SEQ ID NO.11) and 5'-tgacagcttatcatcgataaTTAGTTCTTCCCCGCATATTC-3' (as shown in SEQ ID NO.12) were used as primers. After 30 rounds of PCR reactions, a fragment of 2.5 kb in length was obtained.
[0039] (4) The linearized plasmid and fragment prepared by the above method were digested with NEB's DpnI enzyme and recovered by agarose gel electrophoresis to obtain a single target band.
[0040] (5) Finally, homologous recombination was performed using the ClonExpress® Ultra One Step Cloning Kit from Novezan to obtain the complete circular plasmid pWANGLab-AVS51, as shown in Figure 1 shown; it contains the TIR-STAND codon-optimized gene from Klebsiella pneumoniae strain CTKp47 NODE_7.
[0041] 2. Construction of pWANGLab-AVS52 containing kpTIR-STAND
[0042] (1) Plasmid pQE82L was linearized with NEB's Q5 High-Fidelity 2× Master Mix using primers 5'-taataccccgggtcgacctg-3' (as shown in SEQ ID NO. 13) and 5'-agttaatttctcctctttaatgaattc-3' (as shown in SEQ ID NO. 10) after 30 rounds of PCR to obtain a 4.2 kb linearized plasmid.
[0043] (2) Using the codon-optimized pUC19-kpTIR-STAND (as shown in SEQ ID NO. 4) as a template, NEB's Q5 High-Fidelity 2× Master Mix, and primers 5'-ttaaagaggagaaattaactATGATTAAGGCTTTCCTGAG-3' (as shown in SEQ ID NO. 11) and 5'-caggtcgacccggggtattaGTTCTTCCCCGCATATTC-3' (as shown in SEQ ID NO. 14), a 2.5 kb fragment was obtained after 30 rounds of PCR reactions.
[0044] (3) The linearized plasmid and fragment prepared by the above method were digested with NEB's DpnI enzyme and recovered by agarose gel electrophoresis to obtain a single target band.
[0045] (4) Finally, homologous recombination was performed using the ClonExpress® Ultra One Step Cloning Kit from Novezan to obtain the complete circular plasmid pWANGLab-AVS52, as shown in Figure 2 shown; it contains the TIR-STAND codon-optimized gene from Klebsiella pneumoniae strain CTKp47 NODE_7.
[0046] 3. Construction of pWANGLab-AVS53 containing ecTIR-STAND
[0047] (1) Plasmid pACYC184 was linearized to 4.2 kb after 30 rounds of PCR using NEB's Q5 High-Fidelity 2× Master Mix and primers 5'-gctttaatgcggtagtttatcac-3' (as shown in SEQ ID NO. 7) and 5'-ttatcgatgataagctgtcaaac-3' (as shown in SEQ ID NO. 8).
[0048] (2) Using plasmid pQE82L as a template and NEB's Q5 High-Fidelity 2× Master Mix with primers 5'-ataaactaccgcattaaagctcataaaaaatttatttgctttgtgag-3' (as shown in SEQ ID NO.9) and 5'-agttaatttctcctctttaatgaattc-3' (as shown in SEQ ID NO.10), a 0.12 kb fragment containing the T5-promoter was obtained after 30 rounds of PCR reaction.
[0049] (3) The nucleotide sequence shown in SEQ ID NO.5 (i.e., the nucleotide sequence before optimization of the protein composition containing the TIR domain expressed in Escherichia coli strain CVMN17EC0100 SAMN10221007-rid6731453.denovo.04) was codon optimized. Using the codon-optimized pUC19-ecTIR-STAND (the optimized nucleotide sequence of the protein composition containing the TIR domain expressed is shown in SEQ ID NO.6) as a template, NEB's Q5 High-Fidelity 2× Master Mix was used, and 5'-aaattaactATGATCAAAGCGTTTCTGTCTCACTCTTC-3' (as shown in SEQ ID NO.15) and 5'-tgacagcttatcatcgataaTTAGTTCTTCGCAGCGTATTC-3' (as shown in SEQ ID NO.16) as primers. After 30 rounds of PCR reactions, a fragment of 2.5 kb in length was obtained.
[0050] (4) The linearized plasmid and fragment prepared by the above method were digested with NEB's DpnI enzyme and recovered by agarose gel electrophoresis to obtain a single target band.
[0051] (5) Finally, homologous recombination was performed using the ClonExpress® Ultra One Step Cloning Kit from Novezan to obtain the complete circular plasmid pWANGLab-AVS53, as shown in Figure 3 as shown; it contains the TIR-STAND codon-optimized gene from Escherichia coli strain CVM N17EC0100 SAMN10221007-rid6731453.denovo.04.
[0052] 4. Construction of pWANGLab-AVS54 containing ecTIR-STAND
[0053] (1) Plasmid pQE82L was linearized with NEB's Q5 High-Fidelity 2× Master Mix using primers 5'-taataccccgggtcgacctg-3' (as shown in SEQ ID NO. 13) and 5'-agttaatttctcctctttaatgaattc-3' (as shown in SEQ ID NO. 10) after 30 rounds of PCR to obtain a 4.2 kb linearized plasmid.
[0054] (2) Using codon-optimized pUC19-ecTIR-STAND as a template, NEB's Q5 High-Fidelity 2× Master Mix, and primers 5'-ttaaagaggagaaattaactATGATCAAAGCGTTTCTGTC-3' (as shown in SEQ ID NO. 17) and 5'-tgcaggtcgacccggggtattaGTTCTTCGCAGCGTATTC-3' (as shown in SEQ ID NO. 18), a 2.5 kb fragment was obtained after 30 rounds of PCR reaction.
[0055] (3) The linearized plasmid and fragment prepared by the above method were digested with NEB's DpnI enzyme and recovered by agarose gel electrophoresis to obtain a single target band.
[0056] (4) Finally, homologous recombination was performed using the ClonExpress® Ultra One Step Cloning Kit from Novezan to obtain the complete circular plasmid pWANGLab-AVS54, as shown in Figure 4 shown; it contains the TIR-STAND codon-optimized gene from Klebsiella pneumoniae strain CTKp47 NODE_7.
[0057] Example 2: Plasmids containing TIR-STAND confer host resistance to bacteriophage
[0058] The recombinant vector plasmids pWANGLab-AVS51, pWANGLab-AVS52, pWANGLab-AVS53, and pWANGLab-AVS54 prepared in Example 1 were separately transformed into Escherichia coli E. coli B, E. coli MG1655, and E. coli BL21 (DE3), and engineered strains were obtained by screening for ampicillin or chloramphenicol resistance.
[0059] The engineered strain was cultured overnight at 37°C. The next day, the strain was expanded into 5 mL LB medium at a dilution ratio of 1:100. The medium containing the plasmid pQE82L vector contained 0.1 mM IPTG and was cultured at 37°C until the OD 600 =0.6.
[0060] Take 500 μL of bacterial solution and prepare plates by double-layer plate method. The corresponding plates containing plasmid pQE82L as vector contain 0.1 mM IPTG (isopropyl-β-D-thiogalactopyranoside). Dilute the phage serially (dilution factor is 10 -1, 10 -2 , 10 -3 , 10 -4 , 10 -5 , 10 -6 , 10 -7 ), point board.
[0061] The plate was inverted and placed in a 37°C incubator.
[0062] The next day, the infection of bacteriophages T1, JMPW2, T4, T5, T7, EEP and λ in the strain was observed.
[0063] Figure 5 The figure shows the resistance test results of E. coli B (Empty vector) and E. coli B (kpTIR-STAND, pWANGLab-AVS52) to bacteriophages T4, T5, and T7 at 37°C.
[0064] Figure 6 This figure shows the resistance test results of E. coli MG1655 (Empty vector) and E. coli MG1655 (kpTIR-STAND, pWANGLab-AVS52) to bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ at 37°C.
[0065] from Figure 5 and Figure 6 It can be seen that under the induction of 0.1 mM IPTG, E. coli B containing the kpTIR-STAND system has obvious resistance to bacteriophages T4, T5, and T7 compared with the control group under the same induction conditions, and E. coli MG1655 containing the system has obvious resistance to bacteriophages T1, JMPW2, T4, T5, and T7.
[0066] Figure 7 The figure shows the resistance test results of E. coli BL21 (DE3) (Empty vector) and BL21 (DE3) (kpTIR-STAND, pWANGLab-AVS51) to bacteriophages T1, JMPW2, T4, T5, T7, EEP and λ at 37°C. Figure 7 It can be seen that after the T5 promoter was introduced into the pACYC184 plasmid, BL21 (DE3) containing the kpTIR-STAND system developed obvious resistance to bacteriophage T4 under non-induction conditions, and produced extremely weak resistance to bacteriophage T1, JMPW2, T5, T7, EEP and λ.
[0067] from Figure 8 It can be seen that after the T5 promoter was introduced into the pACYC184 plasmid, E. coli MG1655 containing the kpTIR-STAND system had obvious resistance to bacteriophages T1, JMPW2, T4, T5, and T7 under non-induction conditions.
[0068] We also tested its homologous protein ecTIR-STAND, and the results were as follows Figure 9 and 10 shown.
[0069] from Figure 9 It can be seen that after the T5 promoter was introduced into the pACYC184 plasmid, E. coli MG1655 containing the ecTIR-STAND system developed resistance to bacteriophages T1, JMPW2, T4, T5, T7 and λ under non-induction conditions, among which the resistance to bacteriophages T4, T5 and T7 was more obvious.
[0070] from Figure 10 It can be seen that E. coli MG1655 containing the ecTIR-STAND system has developed resistance to bacteriophages T1, JMPW2, T4, T5, T7, EEP and λ under the induction conditions of IPTG, among which the resistance to bacteriophages T4 and T5 is more obvious.
[0071] Example 3: Detection of host bacteria's resistance to related phages after placing a tag at the N-terminus or C-terminus of the pWANGLab-AVS52 plasmid containing TIR-STAND
[0072] TIR-STAND proteins are relatively sensitive. We used the pWANGLab-AVS52 plasmid as a base and introduced a 6×His tag at the N-terminus of the kpTIR-STAND protein, naming it His-kpTIR-STAND. We also introduced a Strep tag at the C-terminus of the kpTIR-STAND protein, naming it kpTIR-STAND-CStrep.
[0073] The two tag-containing plasmids and the pQE82L plasmid were introduced into E. coli MG1655, and strains were obtained by ampicillin resistance selection. The constructed strains were cultured overnight at 37°C. The next day, the strains were expanded at a 1:100 ratio into 5 mL of LB medium containing 0.1 mM IPTG and cultured at 37°C to an OD600 of 0.6. 500 μL of the bacterial suspension was prepared using the double-layer plating method with 0.1 mM IPTG. Serial dilutions of the phage were then plated. The plates were inverted and incubated at 37°C. The next day, the strains were observed for infection with phages T1, JMPW2, T4, T5, T7, EEP, and λ.
[0074] The results are as follows Figure 11 shown. Figure 11 The figure shows the results of resistance experiments against bacteriophages T1, JMPW2, T4, T5, T7, EEP, and λ in E. coli MG1655 (Empty Vector) and E. coli MG1655 (kpTIR-STAND, pWANGLab-AVS51) at 37°C without induction. In the presence of either an N-terminal His or C-terminal Strep tag, E. coli MG1655 containing kpTIR-STAND showed no resistance to bacteriophages T1, JMPW2, T4, T5, T7, EEP, or λ.
[0075] The above specific embodiments describe the implementation of the present invention in detail, but the present invention is not limited to the specific details of the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the scope of protection of the present invention.
Claims
1. A protein composition, characterized in that It consists of three structural domains: TIR, NTPase and TPR; the amino acid sequence of the TIR domain is shown in the sequence at positions 1-140 in SEQ ID NO.1 or the sequence at positions 1-140 in SEQ ID NO.2, the amino acid sequence of the NTPase domain is shown in the sequence at positions 141-590 in SEQ ID NO.1 or SEQ ID NO.2, and the amino acid sequence of the TPR domain is shown in the sequence at positions 591-824 in SEQ ID NO.1 or SEQ ID NO.
2.
2. The protein composition according to claim 1, characterized in that The amino acid sequence of the protein composition is shown in SEQ ID NO.1 or SEQ ID NO.
2.
3. A nucleic acid molecule, characterized in that The nucleic acid molecule is used to encode and express the protein composition according to claim 1.
4. The nucleic acid molecule according to claim 3, characterized in that The nucleotide sequence of the nucleic acid molecule is shown in any one of SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5, and SEQ ID NO.
6.
5. A recombinant expression vector, characterized in that: The recombinant expression vector includes a gene segment for encoding and expressing the protein composition according to claim 1 or 2, or includes the nucleic acid molecule according to claim 3 or 4.
6. A host cell, characterized in that The host cell is used to express the protein composition according to claim 1 or 2; or, the host cell contains the nucleic acid molecule according to claim 3 or 4; or, the host cell contains the recombinant expression vector according to claim 5.
7. Use of the protein composition according to claim 1 or 2, or the nucleic acid molecule according to claim 3 or 4, or the recombinant expression vector according to claim 5, or the host cell according to claim 6 in the preparation of an antiviral or anti-phage preparation.
8. An anti-phage or anti-viral method not intended for disease diagnosis or treatment, characterized in that: The nucleic acid molecule or recombinant expression vector for expressing the protein composition according to claim 1 or 2 is transferred into cells to be cultured to enhance the resistance of the cells to be cultured to bacteriophage or virus.
9. The method according to claim 8, characterized in that The cells to be cultured are Escherichia coli E. coli B, E. coli MG1655 or E. coli BL21 (DE3); and / or the bacteriophage is bacteriophage T1, JMPW2, T4, T5, T7, EEP, or λ.