Microcapsules containing bacteriophage

Abstract

The present invention relates to the field of defense against bacterial infections by compositions containing bacteriophages. The present invention particularly relates to an antibacterial composition comprising at least one bacteriophage selected from the family Podoviridae, the family Myoviridae, and the family Siphoviridae as an active agent in a liquid core, a gel shell encapsulating the liquid core, which contains the bacteriophage and dispersion colloidal particles of an ultraviolet blocker that is not a soluble antioxidant compound.

Description

Technical Field

[0001] The present invention relates to the field of defense against bacterial infections by compositions containing bacteriophages.

Background Art

[0002] Pathogenic bacteria can infect various hosts such as humans, animals, and plants. Antimicrobial agents can treat bacterial infections by killing bacteria (bactericidal compounds) or by inhibiting the growth of bacteria (bacteriostatic compounds). Generally speaking, antimicrobial agents are antibiotics derived from plants or fungi, bacteria, or fossils (by extraction or chemical synthesis). Antimicrobial agents can also be of animal origin or even of viral origin. In the latter case, the virus is a phage or a bacteriophage that infects bacteria.

[0003] Bacteria can mutate and thereby adapt to their environment and to antimicrobial agents. For this reason, resistance to antibiotics has become a major problem, and the recognition of this resistance has led to the consideration of alternative antibacterial therapies such as bacteriophages. Also, bacteriophages do not have an adverse effect on the commensal flora and quickly adapt to bacterial mutations. And bacteriophages do not infect eukaryotic cells and are harmless when used in humans, animals, fish, or plants.

[0004] In the field of human health, bacteriophage administration was carried out as early as the 1960s (for example, the φX174 phage belonging to the family Micoviridae and infecting Escherichia coli), and it has been shown that the use of these bacteriophages is safe and is particularly applied in cases of antibiotic resistance or to complement antibiotic therapy. Examples include ENT-related infections caused by Pseudomonas aeruginosa such as otitis media, and intestinal infections caused by Escherichia coli.

[0005] In the fields of animal health and nutrition, where there is a tendency to reduce the use of antibiotics, there are real advantages to the use of bacteriophages. For example, in fish farming, when managing pathogens of rainbow trout or salmon, such as Flavobacterium psychrophilum, or the pathogen Yersinia ruckeri that infects salmon. In poultry farming, phage cocktails against Salmonella or Clostridium perfringens are used, such as those developed by Intralytix Inc.

[0006] In the field of plant health, where bacterial infections are a cause of significant economic losses, most existing biological control methods are based on the use of copper, but its toxicity and potential side effects have led to the exploration of other biological control solutions, including the use of bacteriophages.

[0007] Finally, in the agro-food field, bacteriophages may be used to ensure food safety through their ability to suppress the occurrence of pathogens during food processing or on surfaces in contact with food. Without limitation, Listeria, Shigella, Salmonella, Escherichia coli, or Campylobacter jejuni are priority targets in the agro-food industry.

[0008] One of the difficulties in using bacteriophages is that they can be fragile and sensitive to the environment. Bacteriophages have walls composed only of protein, and these walls are thinner and more fragile than those of bacteria. More specifically, extreme pH values of some soils or even ultraviolet light, such as sunlight, are factors to be considered.

[0009] Improving the long-term stability of phages and maintaining their survival rate is a major challenge when envisioning the large-scale use of bacteriophages. Spray drying technology and freeze drying technology exist (Matinkhoo et al., 2011, J Pharm Sci ;100(12):5197-205; Jones et al., 2012, Bacteriophage 2: 208-214; Vandenheuvel et al., 2013, Eur J Pharm Biopharm; 84(3):578-82; Leung et al., 2016, Pharmaceutical research, 33(6), 1486-1496; Leung et al., 2017, International journal of Pharmaceutics, 521(1-2), 141-149). Tests of encapsulation technologies aimed at improving stability during storage, transportation, and spraying have been conducted.

[0010] When searching for a solution intended to protect bacteriophages from external stresses such as pH or ultraviolet light during storage or dispersion, the applicant conducted experiments on the co-drying of bacteriophages and yeast as described in French Patent Application Publication No. 2110984.

[0011] Surprisingly, by encapsulating the bacteriophage used as an active agent within a shell containing dispersion colloidal particles of a type that blocks ultraviolet light, it becomes possible to maintain the survival rate and antibacterial action of the phage. The phage encapsulated in this way efficiently controls pathogenic bacteria that target humans, animals, or plants as an advantage against bacterial pathogens.

Summary of the Invention

[0012] The present invention thus relates to an antibacterial composition comprising at least one bacteriophage selected from the family Podoviridae, Myoviridae, and Siphoviridae as an active agent in a liquid core, wherein the liquid core containing the bacteriophage is encapsulated in a gel shell containing dispersion colloidal particles of an ultraviolet light blocker, and the ultraviolet light blocker is not a soluble antioxidant compound.

[0013] Detailed Description

Embodiments for Carrying Out the Invention

[0014] The terms phage or bacteriophage are used interchangeably. A phage or bacteriophage is a virus that infects bacteria with a high degree of specificity and without any significant side effects on human, animal, or plant hosts. The antibacterial composition that is the subject of the present invention is thus directed against any bacteria that may be pathogenic, regardless of whether the host is human, animal, or plant. Antibacterial action is understood to mean that bacteria undergo lysis after being infected with a bacteriophage.

[0015] In one embodiment, the targeted pathogen is a bacterium that can infect plants and / or harvested products. Bacterial diseases of plants cause significant losses to agricultural and vegetable crops. There are few available treatment methods, and many are copper-based. Iriarte et al. (Bacteriophage, 2012; 2(4): 215 - 224) showed that phages can penetrate inside plants, move from roots to leaves, and remain inside plants for up to 7 days.

[0016] Regarding the above-ground parts of plants, the targeted pathogen is selected from the following: Erwinia species, more specifically Erwinia amylovora; Xanthomonas species, more specifically Xanthomonas axonopodis var. citri, which has citrus as the host and is generally the cause of a disease called citrus canker; Xylella species, more specifically Xylella fastidiosa, which can infect approximately 600 plant species (grapes, yuzu, fruit trees, almond trees, olive trees, cherry trees, coffee trees, avocado trees, alfalfa, poplar, oak, maple, etc.) belonging to more than 80 different plant families. The disease that occurs in grapes is called Pierce's disease.

[0017] In soil diseases that require spraying through a drip system or spraying on seeds, the targeted pathogen is selected from the following: Pseudomonas species, more specifically Pseudomonas syringae pv. tomato, which is the cause of a disease called bacterial speck in tomato plant hosts; Ralstonia species, more specifically Ralstonia solanacearum, which also has tomato plants as the host and is the cause of a disease known as bacterial wilt.

[0018] Regarding the harvested plant products, spraying is carried out directly on the products, and in particular, the targeted pathogens are Pectobacterium and Dickeya, which can infect potato plants.

[0019] Fire blight bacterium (Erwinia amylovora) is a pathogenic plant bacterium that causes fire blight, a contagious disease that affects apple trees, pear trees, and other plants in the Rosaceae family (Momol MT; Aldwinckle HS, 2000. Genetic diversity and host range of Erwinia amylovora. In: Vanneste JL, ed. Fire blight the disease and its causative agent, Erwinia amylovora. Wallingford, Oxon UK: CABI Publishing, 55-72; Zwet T van der; Keil HL, 1979. Fire blight, a bacterial disease of Rosaceous plants. Agriculture Handbook, Science and Education Administration USDA. Beltsville, USA: USDA, No. 510:200 pp). By screening 33 phage groups that infect Erwinia, for example, five phages of the Myoviridae family that can infect a wide range of Erwinia amylovora strains were isolated. The phages, designated BPH1, 31Dx, 26C, P2, and 2By, respectively, were used in the encapsulation test of the antibacterial composition of the present invention.

[0020] In one embodiment, the targeted pathogen is a bacterium that can infect humans. Among these are, but are not limited to, Escherichia coli, Listeria monocytogenes, Campylobacter jejuni, Staphylococcus aureus, Clostridium perfringens, or a strain of the genus Salmonella.

[0021] In one embodiment, the targeted pathogen is a bacterium that can infect animals, such as Escherichia coli, Salmonella, Campylobacter, Staphylococcus, Flavobacterium psychrophilum, Yersinia ruckeri, Clostridium perfringens, etc. The animals to be treated include not only cattle, but also sheep, pigs, poultry, fish, crustaceans, etc.

[0022] In one embodiment, the targeted pathogen is a pathogen for which the agri-food industry seeks protection of dairy products, meat or fish: Listeria, Salmonella, Shigella, Escherichia coli, Campylobacter jejuni, etc.

[0023] As an advantage, by encapsulation, the antibacterial composition of the present invention can maintain its antibacterial property, as shown, for example, by the experimental results described in the following examples. To show the survival rate of phages and to count phages, it is essential that the phages retain their effectiveness against the targeted pathogen.

[0024] The capsules used in the antibacterial composition of the present invention have a shell and are prepared from a solution containing a biopolymer having gelling properties and contain colloidal dispersion particles of an ultraviolet blocker that is not a soluble antioxidant compound.

[0025] The microcapsules used in the antibacterial composition of the present invention can confine bacteriophages, rather than immobilize them.

[0026] Microcapsules are well known to those skilled in the art. Microcapsules can be formed by various methods and can have various shell compositions. Typically, the microcapsules used in the present invention are manufactured according to the manufacturing methods described in French Patent No. 2939012 and International Publication No. 2010063937 (A1) pamphlet.

[0027] The microcapsule consists of a liquid core containing at least one phage that forms the active agent of the antibacterial composition of the present invention. This liquid core may contain a mixture of different phages.

[0028] The liquid core is encapsulated in a gel-like, substantially solid outer coating called a shell. In particular, the shell is solid. Preferably, the shell of the microcapsule is mainly composed of a biopolymer having gelling properties. In particular, the shell is composed of the biopolymer having gelling properties. This biopolymer that occupies a majority ratio in the shell becomes the main biopolymer. The biopolymer having gelling properties is, for example, alginic acid, gellan gum, xanthan gum, pectin, chitosan, agar, or carragheenin. Preferably, the shell of the microcapsule forming the antibacterial composition of the present invention is mainly composed of alginic acid. In particular, the shell is composed of alginic acid.

[0029] In the case of the hydrated form, for example, when suspended in an aqueous solution, the microcapsules of the antibacterial composition of the present invention have an average diameter of 50 to 4000 μm, preferably 100 to 2000 μm, more specifically 200 to 1000 μm, and advantageously 200 to 600 μm. This average diameter can be measured by various methods known to those skilled in the art, such as laser light diffraction, fractionation by screening, or particle size analysis based on imaging by optical microscopy. The microcapsules can also be in a dehydrated form. The dehydration reaction is preferably partial, and the hydrated microcapsules preferably have a moisture level of less than 10% when measured with a moisture meter after the dehydration reaction.

[0030] Preferably, the microcapsules of the present invention are of the independent type. That is, the microcapsules of the present invention are not contained in another structure such as a film, beads, or gel, that is, no second encapsulation is performed, and are in direct contact with the medium surrounding the microcapsules, typically a liquid (for example, in a suspended state) or a gas.

[0031] The colloidal particles of the ultraviolet light blocking agent mean particles having an average size of 10 nm to 10 μm, more preferably 100 nm to 5 μm. Generally, the smaller the particles, the higher the efficiency against ultraviolet light. These blocking agents may also make the microcapsules opaque.

[0032] In the context of the present invention, the UV blocker is not a soluble antioxidant compound. Such compounds tend to decompose more rapidly when exposed to UV light. The UV blocker used in the microcapsules forming the antibacterial composition of the present invention can be an organic or inorganic substance, or a mixture of an organic blocker and an inorganic blocker. The UV blocker is preferably selected from titanium oxide, carbon black, biochar, charcoal, latex, silica, clay, and mixtures thereof. Biochar is a product of biomass pyrolysis and is used in agriculture for soil restoration. The clay used as a UV blocker is, for example, talc, or kaolin, and mixtures thereof. Kaolin is a type of clay and is also used in agriculture to protect some crops from pests.

[0033] Preferably, the UV blocker used in the microcapsules forming the antibacterial composition of the present invention is biodegradable and / or suitable for ingestion and / or pharmaceutically acceptable.

[0034] The "dispersed particles of the UV blocker" means particles that are preferably dispersed in the shell of the microcapsule in order to provide a uniform UV protection effect on the surface of the microcapsule. Preferably, the core of the capsule of the present invention does not contain particles of the UV blocker. In particular, the concentration of the UV blocker is 0.05 - 30 v / v%, more specifically 0.1 - 20 v / v% with respect to the total volume of the shell.

[0035] Preferably, in the method and use of the present invention, the microcapsules are used as such, i.e., not contained in another structure (film, beads, gel, or second encapsulation, etc.) and are used as they are, optionally suspended in a liquid as desired.

[0036] The present invention also relates to a method for protecting and / or treating a plant from at least one pathogenic bacterium, comprising Providing an antibacterial composition comprising, as an active agent against said at least one pathogenic bacterium, at least one bacteriophage, said bacteriophage being protected from ultraviolet light in microcapsules containing colloidal particles of an ultraviolet blocker dispersed in a shell, said ultraviolet blocker not being a soluble antioxidant; Applying said composition to the aerial parts of said plant; relates to a method comprising.

[0037] In particular, said at least one bacteriophage is selected from the families Podoviridae, Myoviridae, and Siphoviridae.

[0038] In one embodiment, the harvested product of said plant is subjected to prevention and / or treatment for antibacterial purposes.

[0039] In one embodiment, the antibacterial composition can also be applied by spraying on the soil. In another embodiment, the antibacterial composition can be applied around the seeds, particularly not only by coating or filming. In another embodiment, the application can be carried out on the post-harvest product.

[0040] In another embodiment, the present invention relates to the non-therapeutic use of the antibacterial composition of the present invention, preferably for the nutrition and / or nourishment of animals and / or humans. In this embodiment, the phages used are preferably not therapeutic phages. In other words, said phages are interesting from a nutritional or nourishing point of view, but cannot prevent or treat the diseases of the animals or individuals ingesting these phages.

[0041] "Nourishment" means normal or frequent food intake. The antibacterial composition may contain various phages that can improve the properties of food, and these properties may include bioavailability or storage time.

[0042] "Nutrition" in most cases means the intake of dietary supplements, typically to prevent or compensate for deficiencies, during a temporary or convalescent period. The antibacterial composition of the present invention can contain various phages that can improve nutrient intake by improving its bioavailability or can modify the intestinal flora.

[0043] The present invention also relates to a pharmaceutical composition comprising the antibacterial composition of the present invention.

[0044] The present invention also relates to the antibacterial composition or pharmaceutical composition of the present invention for use as an antibacterial agent, particularly for use as a pharmaceutical, more specifically for use in the treatment of diseases caused by bacteria, in a subject in need thereof. In this embodiment, the antibacterial composition of the present invention advantageously comprises a phage selected from bacteriophages that target pathogenic bacteria in humans or animals, more specifically, a bacteriophage that targets bacteria selected from strains of Escherichia coli, Listeria monocytogenes, Campylobacter jejuni, Staphylococcus aureus, Clostridium perfringens, or Salmonella.

[0045] The term "pharmaceutical composition" as defined herein refers to a mixture or solution containing at least one therapeutic agent administered to a subject for the prevention or treatment of a specific disease from which the subject is suffering.

[0046] Thus, a pharmaceutical composition as defined herein additionally and preferably contains pharmaceutically acceptable excipients.

[0047] As used herein, "pharmaceutically acceptable" means that the compositions and molecular entities do not produce a secondary reaction, allergic reaction, or other adverse reaction when administered to a subject.

[0048] As used herein, "subject" means an organism, preferably a mammal, more specifically a human.

[0049] As used herein, "therapeutically effective amount" means the dosage and duration necessary to obtain a desired therapeutic result. This amount may vary depending on factors such as the disease, the degree of the disease, the age, sex, and weight of the subject, and the ability of the microcapsules to induce the desired therapeutic result. A therapeutically effective amount includes an amount where the beneficial effects of treatment offset any toxic or adverse effects. A therapeutically effective amount also includes an amount sufficient to confer a benefit, such as a clinical benefit.

[0050] The pharmaceutical composition is preferably adapted to the route of administration.

[0051] In one particular embodiment, the pharmaceutical composition is adapted for oral administration, sublingual administration, buccal administration, intranasal administration, or topical administration.

[0052] As described above, the present invention also relates to the antibacterial composition or pharmaceutical composition of the present invention for use as a medicament. The present invention also relates to the antibacterial composition of the present invention for use in the formulation of a pharmaceutical composition.

[0053] For these uses, the antibacterial composition of the present invention advantageously comprises a phage selected from bacteriophages targeting human or animal pathogenic bacteria, more specifically a bacteriophage targeting bacteria selected from strains of Escherichia coli, Listeria monocytogenes, Campylobacter jejuni, Staphylococcus aureus, Clostridium perfringens, or Salmonella.

[0054] Using the antibacterial composition of the present invention facilitates the storage, packaging, or preparation of pharmaceutical compositions while preserving the active phage.

[0055] As used herein, "treating" or "treatment" means partially or substantially obtaining one or more of the following results: partial or complete reduction in the degree of disease, improvement in clinical symptoms or markers associated with the disease, delay, inhibition, or prevention of disease progression. In particular, in the present invention, the disease to be treated is a disease caused by bacteria, particularly the bacteria mentioned above.

[0056] The following examples are for illustrative purposes only and should not be construed as limiting the scope of the present invention.

Examples

[0057] Example

[0058] Phage counting method Methods for bacteriophage survival rate and counting always use bacteria targeted by the test bacteriophage. Generally, the counting method for bacteriophages of unknown concentration is the semi-solid agar overlay method known to those skilled in the art. A preculture of the target bacteria was obtained in liquid LB medium (Luria-Bertani broth). In some cases, the preculture step in the liquid medium may be doubled to reach a sufficient volume and concentration, and the concentration is evaluated by OD measurement (absorbance) at 600 nm. Serial dilutions of the phages to be counted were performed in liquid LB medium. The contact between the serial dilutions of the phages and the bacterial culture was carried out on LBA medium (Luria-Bertani agar) pre-added with Luria-Bertani agar semi-solidified with 0.75% agar. After incubation at 30 °C for 16 - 24 hours, the lysis zones were read and counted.

[0059] For the counting of anti-Salmonella phage (SalmoFresh (trademark)) supplied by Intralytics, Salmonella Newport strain was used. For the counting of anti-Listeria phage supplied by Intralytics, Listeria monocytogenes strain was used. For the counting of anti-Erwinia phages (BPH1 phage, 31Dx phage, 26C phage, P2 phage, and 2By phage), Erwinia amylovora Ea4 strain supplied by INRAe was used.

[0060] Example 1: Evaluation of Phage Encapsulation Test and Stability after Encapsulation

[0061] The phage BPH1 was encapsulated in capsules containing no UV blocker. Drying tests were performed using three different drying substrates. The long-term survival rate and stability as a function of temperature were evaluated.

[0062] Among glycerol, SM-sucrose, and trehalose tested as drying excipients, SM-sucrose was the excipient that gave the most acceptable drying yield.

[0063] The stability of the encapsulated phages was tested at +4°C, +25°C, and +40°C for 1 month each. At +4°C or +25°C, the encapsulated phages in liquid form had a very small decrease in titer. At +40°C, the titer decreased by about 2 logarithms. In the solid form, i.e., after drying with SM-sucrose as the excipient, the titer remained almost the same regardless of the storage temperature, and the decrease at +40°C was less than 1 logarithm.

[0064] Example 2: Protection of anti-Erwinia phages in capsules containing ultraviolet blockers

[0065] The above BPH1 phage, 31Dx phage, 26C phage, P2 phage, and 2By phage were encapsulated in a shell containing biochar as an anti-ultraviolet blocker. Phage alone, capsule + phage containing biochar, or capsule + phage without biochar in liquid form were exposed to ultraviolet light. These phages were deposited in the Collection Nationale de Cultures de Microorganismes, which is stored at the Institut Pasteur (25 rue du docteur Roux, 75015 Paris, France) based on the Budapest Treaty: BPH1 was deposited on December 17, 2021, under the number I-5803, 31Dx was deposited on May 6, 2022, under the number I-5845, 26C was deposited on May 6, 2022, under the number I-5846, P2 was deposited on May 6, 2022, under the number I-5847, 2By was deposited on May 6, 2022, under the number I-5848.

[0066] The ultraviolet exposure protocol was as follows: Using a sterile cell strainer, collect a uniform sample consisting of capsules sized 100 μm; Sampling 3 g of wet capsules or 1 g of dry capsules respectively, and sieving them into a sterile Petri dish; Add 0.1 M NaCl buffer diluted 1:10 with sterile saline; Remove the control before exposure; Expose to ultraviolet rays with an intensity of 105 mW / cm 2 using a preheated lamp if necessary. Place the Petri dish in the center of the dryer. The exposure times are 10 minutes, 20 minutes, and 30 minutes respectively for non-encapsulated phages, encapsulated phages in the absence of a UV blocker, encapsulated phages in the presence of a UV blocker, and the control NaCl buffer. For counting, 200 μL of the sample was taken after UV exposure. Prior to performing the counting as described above, remove as much supernatant as possible, measure the weight of the capsules, open them by adding 1 mL of PBS EDTA, place them under stirring at medium speed for 5 minutes with a rotary disk stirrer, perform serial dilution, and conduct the counting according to the above protocol.

[0067] Table 1 shows the titer results of phage BPH1 after UV exposure times of 0 minutes, 5 minutes, 10 minutes, 20 minutes, and 30 minutes respectively. LDD is the detection limit.

[0068]

Table 1

[0069] These results show that after 5 minutes of UV exposure, the phage titer decreased sharply (>4 logarithms) at the same rate as the "free" phage used as a control. Conversely, in the case of phages encapsulated with biochar, the decrease in titer is smaller: from a 1-log titer decrease after 5 minutes to a 2-log titer decrease after 30 minutes of exposure. These results clearly show that capsules containing biochar efficiently protect phages from inactivation.

[0070] As shown in Table 2, similar results were obtained when encapsulated and dried phages were exposed to ultraviolet light after rehydration, with an exposure time of 10 minutes.

[0071]

Table 2

[0072] Tables 3 and 4 show the titration results of the 31Dx phage after ultraviolet exposure times of 0, 5, 10, 20, and 30 minutes, respectively. LDD indicates the detection limit for each of the wet and dry capsules.

[0073]

Table 3

[0074]

Table 4

[0075] Tables 5 and 6 show the titer results of the 26C phage after ultraviolet exposure times of 0, 5, 10, 20, and 30 minutes, respectively. LDD indicates the detection limit for each of the wet and dry capsules.

[0076]

Table 5

[0077]

Table 6

[0078] Tables 7 and 8 show the titer results of phage P2 after ultraviolet exposure times of 0 minutes, 5 minutes, 10 minutes, 20 minutes, and 30 minutes, respectively. LDD is the detection limit for each of the wet and dry capsules. NA indicates non-applicable (data not available for technical reasons).

[0079]

Table 7

[0080]

Table 8

[0081] Tables 9 and 10 show the titer results of phage 31Dx after ultraviolet exposure times of 0 minutes, 5 minutes, 10 minutes, 20 minutes, and 30 minutes, respectively. LDD is the detection limit for each of the wet and dry capsules.

[0082]

Table 9

[0083]

Table 10

[0084]

Table 11

[0085]

Table 12

[0086] These results indicate that after a 10-minute ultraviolet exposure time, the number of phages decreased significantly in the free phage control (i.e., non-encapsulated), while the survival rate was preserved in the capsules containing the ultraviolet blocker. Since the survival rate is shown through the antibacterial action of the phages against the target bacteria, these results demonstrate the stability of the antibacterial composition of the present invention.

Claims

1. The active agent in the liquid core is at least one bacteriophage selected from the families Podoviridae, Myoviridae, and Siphoviridae. A gel-like shell containing the liquid core, comprising the bacteriophage and dispersed colloidal particles of an ultraviolet blocking agent that is not a soluble antioxidant compound, An antimicrobial composition containing the above.

2. The antimicrobial composition according to claim 1, wherein the ultraviolet blocking agent is selected from titanium dioxide, carbon black, biochar, charcoal, latex, silica, clay, and mixtures thereof.

3. The composition according to claim 1 or claim 2, wherein the bacteriophage targets at least one pathogenic plant bacterium.

4. The composition according to claim 3, wherein the at least one plant pathogenic bacterium is selected from the species of Erwinia, Xanthomonas, Xylella, Pseudomonas, and Ralstonia.

5. The composition according to claim 4, wherein the plant pathogenic bacterium is a plant pathogenic bacterium of the genus Erwinia.

6. The composition according to claim 1 or claim 2, wherein the bacteriophage targets at least one pathogenic bacterium that may infect humans.

7. The composition according to claim 1 or claim 2, wherein the bacteriophage targets at least one animal pathogenic bacterium.

8. The composition according to claim 1 or claim 2, wherein the bacteriophage targets at least one pathogenic bacterium that may contaminate products of the agrifood industry.

9. Use of the antimicrobial composition according to claim 1 for the treatment of plant crops, their seeds, or harvested products.

10. Use of the antimicrobial composition according to claim 1 for soil treatment.

11. A method for protecting and / or treating a plant from at least one pathogenic bacterium, comprising the steps of: providing an antimicrobial composition comprising at least one bacteriophage as an active agent against the at least one pathogenic bacterium, wherein the bacteriophage is protected from ultraviolet light in a core of a microcapsule containing colloidal particles of an ultraviolet-blocking agent dispersed in a shell enclosing the core, and the ultraviolet-blocking agent is not a soluble antioxidant compound; and applying the composition by spraying it on the above-ground parts of the plant and / or on the ground, or by applying it around seeds.

12. Use of the antimicrobial composition according to claim 1 for human nutrition and / or food.

13. Use of the antimicrobial composition according to claim 1 for animal nutrition and / or feed.

14. A pharmaceutical composition comprising the antibacterial composition according to claim 1 or 2.

15. The composition according to claim 14 for use in the treatment of mammals.