WO2023188945A1 - 新規な抗真菌剤 - Google Patents

新規な抗真菌剤 Download PDF

Info

Publication number
WO2023188945A1
WO2023188945A1 PCT/JP2023/005404 JP2023005404W WO2023188945A1 WO 2023188945 A1 WO2023188945 A1 WO 2023188945A1 JP 2023005404 W JP2023005404 W JP 2023005404W WO 2023188945 A1 WO2023188945 A1 WO 2023188945A1
Authority
WO
WIPO (PCT)
Prior art keywords
strain
genus
acidipila
accession number
fungi
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2023/005404
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
雅親 高田
博文 砂原
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Murata Manufacturing Co Ltd
Original Assignee
Murata Manufacturing Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Murata Manufacturing Co Ltd filed Critical Murata Manufacturing Co Ltd
Priority to CN202380010874.2A priority Critical patent/CN117157408A/zh
Priority to EP23778975.5A priority patent/EP4310190A4/en
Priority to JP2023530585A priority patent/JP7568100B2/ja
Publication of WO2023188945A1 publication Critical patent/WO2023188945A1/ja
Priority to US18/505,399 priority patent/US20240081339A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/20—Bacteria; Substances produced thereby or obtained therefrom
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
    • C12P1/04—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using bacteria
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales

Definitions

  • the present invention relates to an antifungal substance derived from bacteria of the genus Acidipila.
  • Non-patent Document 1 A significant number of naturally occurring pharmaceuticals are actually produced by microorganisms. This shows that the search for natural products derived from microorganisms is extremely important in drug development.
  • actinomycetes are a group of microorganisms that have received the most attention as a source of new drug discovery since the discovery of streptomycin. Actinomycetes have many biosynthetic genes related to secondary metabolites and are known as a bacterial group that produces chemically diverse secondary metabolites. There are hundreds of antibiotic compounds derived from actinomycetes that have been put to practical use, making them the most important taxonomic group as a source of natural product exploration.
  • the present invention aims to provide novel antifungal compounds by searching for a new group of culturable microorganisms that produce a wide variety of secondary metabolites.
  • actinobacteria have been the main source for searching for natural products for pharmaceuticals, but the present inventors have newly focused on bacteria of the phylum Acidobacteria, which have a high ability to produce secondary metabolites. .
  • Bacteria of the phylum Acidobacterium are mostly Gram-negative bacteria that exist in soil and are difficult to cultivate, so most of them are uncultured microorganisms.
  • the present inventors surprisingly discovered that among bacteria of the phylum Acidobacterium, bacteria of the genus Acidipila produce antifungal substances.
  • the present inventors isolated a novel Acidipyra bacterium. Thus, the present invention was completed.
  • the present invention provides, for example, the following aspects.
  • Acidipila bacteria are Acidipila sp.
  • the MT3 strain accession number NITE BP-036114
  • the MT4 strain accession number NITE BP-03615
  • the MT5 strain accession number NITE BP-03616 strain
  • Antifungal agents listed are listed.
  • the yeast is selected from the group consisting of fungi of the genus Saccharomyces, fungi of the genus Candida, fungi of the genus Malassezia, and fungi of the genus Rhodotorula.
  • the antifungal agent according to any one of [1] to [4], wherein the antifungal substance derived from bacteria of the genus Acidipila is a culture or culture supernatant of bacteria of the genus Acidipila, or a concentrate or extract thereof.
  • a method for producing an antifungal agent targeting yeast or filamentous fungi which comprises culturing Acidipila bacteria.
  • Acidipila bacteria are Acidipila sp.
  • the MT3 strain (accession number NITE BP-03614), the MT4 strain (accession number NITE BP-03615), the MT5 strain (accession number NITE BP-03616), or the MT6 strain (accession number NITE BP-03617), [6] Method described. [8] The method according to [6] or [7], wherein the filamentous fungus is selected from the group consisting of fungi of the genus Aspergillus, fungi of the genus Mucor, and fungi of the genus Trichophyton.
  • yeast is selected from the group consisting of fungi of the genus Saccharomyces, fungi of the genus Candida, fungi of the genus Malassezia, and fungi of the genus Rhodotorula.
  • Acidipila sp. strain MT3 (accession number NITE BP-03614), strain MT4 (accession number NITE BP-03615), strain MT5 (accession number NITE BP-03616), or strain MT6 (accession number NITE BP-03617).
  • a method for inhibiting the growth of a fungus wherein the fungus is yeast or a filamentous fungus, and the method comprises contacting the yeast or filamentous fungus with an antifungal substance derived from a bacterium of the genus Acidipila.
  • Acidipila bacteria are Acidipila sp.
  • the MT3 strain accession number NITE BP-036114
  • the MT4 strain accession number NITE BP-03615
  • the MT5 strain accession number NITE BP-03616)
  • the MT6 strain accession number NITE BP-03617
  • filamentous fungus is selected from the group consisting of fungi of the genus Aspergillus, fungi of the genus Mucor, and fungi of the genus Trichophyton.
  • yeast is selected from the group consisting of fungi of the genus Saccharomyces, fungi of the genus Candida, fungi of the genus Malassezia, and fungi of the genus Rhodotorula.
  • the MT3 strain (accession number NITE BP-03614), the MT4 strain (accession number NITE BP-03615), the MT5 strain (accession number NITE BP-03616), or the MT6 strain (accession number NITE BP-03617), [16] Use as described. [18] The use according to [16] or [17], wherein the filamentous fungus is selected from the group consisting of fungi of the genus Aspergillus, fungi of the genus Mucor, and fungi of the genus Trichophyton.
  • yeast is selected from the group consisting of fungi of the genus Saccharomyces, fungi of the genus Candida, fungi of the genus Malassezia, and fungi of the genus Rhodotorula.
  • a novel antifungal substance derived from bacteria of the genus Acidipila is provided.
  • the antifungal substance is useful, for example, as an active ingredient in pharmaceuticals for treating diseases caused by fungi, cosmetics, cleaning agents, food additives (preservatives, etc.), disinfectants, and the like.
  • the antifungal substance of the present application is a substance produced by bacteria of the genus Acidipila as a secondary metabolite.
  • Antifungal substances are substances that have antifungal activity.
  • antifungal activity refers to the ability to suppress or inhibit the growth of fungi. Antifungal activity can be confirmed by methods known in the art. Known methods include, for example, the Spot-on-lawn method, the Direct method, the paper disk method, and the MIC (minimum inhibitory concentration) method.
  • the fungi targeted by the antifungal substance of the present application are not particularly limited.
  • the antifungal substance of the present application has antifungal activity against various fungi including various yeasts and filamentous fungi. Preferably, it has antifungal activity against yeast and filamentous fungi.
  • yeast include, but are not limited to, Saccharomyces, Zygosaccharomyces, Candida, Cryptococcus, Malassezia, Rhodotorula, Pneumocystis.
  • yeast include, but are not limited to, Saccharomyces, Zygosaccharomyces, Candida, Cryptococcus, Malassezia, Rhodotorula, Pneumocystis.
  • yeast include, but are not limited to, Saccharomyces, Zygosaccharomyces, Candida, Cryptococcus, Malassezia, Rhodotorula, Pneumocystis.
  • yeast examples include, but are not limited to, Saccharomyces cerevisiae, Zygosaccharomyces rouxii, Candida albicans, Candida glabrata, Candida tropicalis, Candida auris, Cryptococcus neoformans, Malassezia furfur, Rhodotorula glutini, Pneumocystis jirovecii, etc., and are preferred.
  • Saccharomyces cerevisiae Candida albicans, Candida glabrata, Candida tropicalis, Malassezia furfur, and Rhodotorula glutini.
  • filamentous fungi examples include, but are not limited to, the genus Trichophyton, the genus Aspergillus, the genus Mucor, the genus Penicillium, the genus Chaetomium, and the genus Cladophyton.
  • filamentous fungi examples include, but are not limited to, the genus Trichophyton, the genus Aspergillus, the genus Mucor, the genus Penicillium, the genus Chaetomium, and the genus Cladophyton.
  • Examples include microorganisms of the genus Cladosporium, genus Aureobasidium, genus Gliocladium, genus Paecilomyces, and preferably microorganisms of the genus Trichophyton, Mucor, and Aspergillus. Examples include microorganisms.
  • filamentous fungi include, but are not limited to, Trichophyton rubrum, Trichophyton mentagrophytes, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, Mucor mucedo, Penicillium funiculosum, Chaetomium globosum, Cladosporium cladosporioides, Aureobasidium pullulan.
  • Trichophyton rubrum Trichophyton mentagrophytes
  • Aspergillus niger Aspergillus flavus
  • Aspergillus fumigatus Aspergillus terreus
  • Mucor mucedo preferably Trichophyton rubrum, Trichophyton mentagrophytes, Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Aspergillus terreus, and Mucor mucedo.
  • the bacteria belonging to the genus Acidipyla may be any species or strain belonging to the genus Acidipyla.
  • known bacterial species such as, but not limited to, Acidipila dinghuensis and Acidipila rosea may be used.
  • freshly isolated bacteria of the genus Acidipyra may be used.
  • Bacteria of the genus Acidipila can be isolated, for example, from soil, and isolation and selection methods may be performed according to known methods or can be determined as appropriate by those skilled in the art. For example, but not limited to, Medium 1426 ("SSE/HD 1:10" medium) published by DSMZ (German Collection of Microorganisms and Cell Cultures) GmbH, etc.
  • the culture may be carried out at 24 hours to 30 days at 28°C to 35°C, preferably 7 to 14 days at 28°C to 30°C.
  • the culture conditions may be appropriately determined by those skilled in the art depending on the appearance and growth status of the bacterial cells.
  • bacteria of the genus Acidipila produce an antifungal substance. Therefore, the bacteria of the genus Acidipila used in this application have the ability to produce antifungal substances.
  • Acidipila sp four new strains of bacteria of the genus Acidipyra were isolated and identified as new species. Acidipila sp. They were named MT3 strain, MT4 strain, MT5 strain, and MT6 strain and submitted to the National Institute of Technology and Evaluation, Patent Microorganisms Depositary (2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan) on March 1, 2022. (accession numbers NITE BP-03614, accession numbers NITE BP-03615, accession numbers NITE BP-03616, and accession numbers NITE BP-03617, respectively). Accordingly, in one embodiment of the present application, Acidipila sp. The MT3 strain, MT4 strain, MT5 strain, or MT6 strain is used.
  • the antifungal substance of the present application is a secondary metabolite produced by culturing Acidipyra bacteria.
  • the method for culturing Acidipila bacteria is not particularly limited, and may be either liquid culture or solid culture, but preferably liquid culture is used.
  • the medium used for culture may be any general medium used for bacterial culture, for example, but not limited to, the medium published by DSMZ (German Collection of Microorganisms and Cell Cultures) GmbH. 1426( "SSE/HD1:10" medium), etc.
  • the culture temperature and culture time may be appropriately determined by a person skilled in the art and are not particularly limited. Good too.
  • the antifungal substance of the present application can be obtained from a culture or culture supernatant of bacteria of the genus Acidipila, and may also be a culture or culture supernatant of bacteria of the genus Acidipila itself, or a concentrate or extract thereof.
  • Culture supernatant can be obtained by conventional methods. For example, it may be obtained by removing bacterial cells from a bacterial cell culture by centrifugation or the like. The culture supernatant may be further subjected to concentration, extraction, and/or purification steps.
  • Concentration, extraction and purification steps can be carried out by conventional methods, such as vacuum concentration, various types of filtration such as filter filtration and ultrafiltration, extraction with organic solvents such as methanol, column chromatography, high performance liquid chromatography, etc. Various chromatography methods, liquid-liquid extraction using chloroform or ethyl acetate, etc. may be used. For purification, distillation, back extraction, column chromatography, recrystallization, etc. may be used.
  • the present application further provides an antifungal agent containing the antifungal substance of the present application as an active ingredient.
  • Antifungal agents are in the form of compositions, such as pharmaceutical compositions, cosmetic compositions (e.g. shampoos, conditioners, bath additives, etc.), cleaning compositions (e.g. household cleaners, laundry detergents, soaps, etc.) ), food additive compositions, disinfectant compositions (for example, applicable to foods, cooking utensils, walls and floors of buildings such as hospitals, and furniture such as desks), and the like.
  • the antifungal agent may contain additional components such as pharmaceutically or foodlogically acceptable carriers, excipients, solvents, stabilizers, and solubilizers.
  • the antifungal agent may further contain other antifungal substances in addition to the antifungal substances of the present application.
  • the antifungal agent may be in any dosage form and may be appropriately selected depending on the purpose of use. Examples include, but are not limited to, lotions, creams, poultices, ointments, tablets, powders, capsules, granules, syrups, infusions, injections, granules, powders, solutions, suspensions, pastes, Examples include dosage forms such as sprays and blocks.
  • the antifungal agent is a pharmaceutical composition, it can be used as a therapeutic or preventive agent for fungal diseases.
  • fungal diseases include cutaneous mycoses and deep mycoses, including, but not limited to, ringworm, Malassezia dermatitis, candidiasis, cryptococcosis, aspergillosis, and zygomycosis. , pneumocystis, and the like, and preferably ringworm, Malassezia dermatitis, candidiasis, aspergillosis, and zygomycosis.
  • the administration route of the pharmaceutical composition may be appropriately selected depending on the therapeutic purpose, and includes, but is not limited to, oral administration, transdermal administration, nasal administration, administration by injection, and the like.
  • the dosage of the pharmaceutical composition is appropriately determined by those skilled in the art.
  • the antifungal agent of the present application when used in a cosmetic composition or a food additive composition, it can be used, for example, as a preservative.
  • the antifungal agent of the present application when used is a cleaning composition or a disinfectant composition, it can be used to prevent fungal infections in buildings and residential equipment (e.g., walls, floors, water areas such as bathrooms, etc.), cooking utensils, laundry, etc. can be used for the removal and prevention of
  • the amount of antifungal agent to be used can be determined as appropriate depending on the purpose of use, usage conditions, and the like.
  • the antifungal substance of the present application may be used in any situation where suppression of fungal growth is required, and by bringing the antifungal agent into contact with the fungus, the growth of the fungus is suppressed. Accordingly, the present application provides a method for inhibiting the growth of a fungus, which comprises contacting the fungus with an antifungal substance derived from a bacterium of the genus Acidipila.
  • "suppression” includes suppressing or inhibiting fungal growth, and/or killing fungi. Examples of situations where suppression of fungal growth is required include, but are not limited to, treatment or prevention of diseases caused by fungi such as mycosis, and prevention of fungal contamination, deterioration, or spoilage of foods, cosmetics, etc. , removal or prevention of fungal contamination of housing and building equipment, cooking utensils, laundry, etc.
  • the method of bringing the antifungal substance into contact with the fungus is appropriately selected depending on the intended use of the antifungal substance (i.e., the situation where suppression of the growth of the fungus is required), and includes, but is not limited to, the method of bringing the antifungal substance into contact with the fungus.
  • the target to be treated is appropriately selected depending on the intended use of the antifungal substance.
  • the antifungal substance may be administered to animals such as humans, or for the purpose of preventing fungal contamination, deterioration, or spoilage of foods, cosmetics, etc.
  • the antifungal substance may be the antifungal agent or may be in the form of the composition.
  • an effective amount of the antifungal substance or antifungal agent is administered, added, applied, sprayed, immersed, etc. to the subject.
  • a method for treating or preventing a mycosis which comprises administering to a patient an effective amount of an antifungal substance derived from a bacterium of the genus Acidipila or an antifungal agent containing the antifungal substance.
  • Another aspect of the present application provides for preventing contamination, deterioration, or spoilage of food or cosmetics, comprising adding an effective amount of an antifungal substance derived from Acidipila bacteria or an antifungal agent containing the antifungal substance to food or cosmetics.
  • a method is provided.
  • an effective amount of an antifungal substance derived from Acidipila bacteria or an antifungal agent containing the antifungal substance is added, applied, sprayed, or dipped into equipment of a house or building, cooking utensils, laundry, etc.
  • methods for removing or preventing fungal contamination of housing and building equipment, cooking utensils, laundry, etc. including:
  • Example 1 Identification of novel Acidipyla bacteria
  • the genome sequences of four strains of Acidipyla bacteria isolated from soil were determined by conventional methods, and 16S rDNA analysis, whole genome analysis, and ANI (Average Nucleotide Identity) analysis were performed. .
  • a species is considered to be a new species if it has a homology rate of 98.7% or less in 16S rDNA analysis and an ANI value of 95% or less in ANI analysis.
  • Isolation of bacterial cells from soil was performed at 30°C on a 1.5 wt% agar medium of Medium 1426 "SSE/HD 1:10" medium published by DSMZ (German Collection of Microorganisms and Cell Cultures) GmbH. 2 This was done by culturing for weeks.
  • ⁇ 16S rDNA analysis> The bacterial cells were lysed with achromopeptidase (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd.), DNA was extracted by a standard method, and PCR amplified using PrimeSTAR HS DNA Polymerase (manufactured by Takara Bio), followed by BigDye Terminator v3.1 Cycle Sequencing K. it (manufactured by Applied Biosystems) to perform cycle sequencing, and the base sequence was determined by ChromasPro 1.7 (manufactured by Technelysium).
  • ANI analysis> ANI values were calculated using EZbiocloud (https://www.ezbiocloud.net/tools/ani), and homology analysis between strains was performed.
  • EZbiocloud https://www.ezbiocloud.net/tools/ani
  • homology analysis between strains was performed.
  • the genome sequence of the target strain is fragmented into 1,020 bp fragments on a computer, and each fragment is searched for homology against the genome sequence of the comparison strain, and the ANI between the genome sequences is calculated from the average of these homology values. Find the value.
  • Example 2 Cultivation of Acidipila bacteria in production medium and preparation of culture concentrate
  • a medium for antifungal substance production was prepared, 100 mL each was dispensed into 500 mL Erlenmeyer flasks, and sterilized in an autoclave at 121°C/20 min. . After the autoclave treatment, 1 mL of each bacterial strain liquid cultured in advance was added. This work was performed under sterile conditions in a safety cabinet. Secondary metabolites were produced by culturing with stirring in a shaker at 27° C. and 210 rpm for 6 days. Thereafter, an equal amount (100 mL) of methanol was added to the culture solution, and the mixture was stirred at 210 rpm for 30 minutes.
  • a bacterial strain Acidipila sp.
  • the MT3 strain, MT4 strain, MT5 strain, and MT6 strain were used as a bacterial strain.
  • YD medium 1% glucose, 1% yeast extract
  • the medium 1426 medium described above was used for culturing for antifungal substance production at 28° C. for 14 days.
  • Example 3 Antifungal activity test (Spot-on-lawn assay) Saccharomyces cerevisiae (NBRC10505) was used as a test bacterium.
  • the cells were inoculated into an MRS (manufactured by Becton, Dickinson and Company) liquid medium and cultured with stirring at 30° C. and 150 rpm for 1 day to prepare a test bacterial solution.
  • 7 mL of MRS soft agar medium (agar 0.5%) was dispensed into test tubes, sterilized in an autoclave (105°C/10 minutes), and cooled to 55-60°C. 70 ⁇ L of the test bacterial solution cultured in the above liquid medium was added to each soft agar medium and stirred using a stirrer.
  • the soft agar medium was poured onto a previously prepared MRS agar plate (1.5% agar) to prepare a medium for antifungal activity testing. An address on the plate was determined, and 10 ⁇ L of the culture concentrate sample obtained in Example 2 was spotted. The cells were cultured at 30°C for 24 hours and visually observed. In this experiment, a zone of inhibition can be seen if there is antifungal activity.
  • Example 4 Test of antifungal activity against various fungi Candida albicans, Malassezia furfur, and Rhodotorula glutini were used as yeast test bacteria. As filamentous fungi, Trichophyton rubrum, Aspergillus niger, and Mucor mucedo were used. Candida albicans, Aspergillus niger, and Mucor musede are known pathogens of the deep mycoses candidiasis, aspergillosis, and zygomycosis, respectively. Malassezia furfur and Trichophyton rubrum are known as pathogens of the skin fungal diseases Malassezia dermatitis and ringworm, respectively. Although Rhodotorula gratinis is not pathogenic, it is known as a red mold that can be found in bathrooms and other water areas.
  • test bacterium was inoculated into each liquid medium and cultured with stirring at 30°C and 150 rpm for 1 day to prepare a test bacterium solution.
  • 7 mL of soft agar medium (0.5% agar) with specifications for each test bacteria was dispensed into test tubes, sterilized in an autoclave (105°C/10 minutes), and cooled to 55-60°C.
  • 70 ⁇ L of the test bacterial solution cultured in the above liquid medium was added to each soft agar medium and stirred using a stirrer.
  • the above-mentioned soft agar medium was poured onto a previously prepared agar medium plate (agar 1.5%) to prepare a medium for antifungal activity test.
  • the composition of the liquid medium used for each test bacteria is shown in Table 2.
  • a paper disk with a diameter of 5 mm was placed on each medium for antifungal activity testing, and 50 ⁇ L of the culture concentrate sample obtained in Example 2 was spotted (paper disk method). The cells were cultured at 30°C for 24 hours and visually observed. Furthermore, a hole of ⁇ 5 mm was made in each medium for antifungal activity testing, and 250 ⁇ L of the culture concentrate sample obtained in Example 2 was spotted (agar well diffusion method). The cells were cultured at 30°C for 24 hours and visually observed. In both experiments, a zone of inhibition can be seen if there is antifungal activity. If an inhibition circle was visually observed, the dimensions of the inhibition circle were measured.
  • the dimension of the inhibition circle is from the outer periphery of the paper disc (for paper disc method) or hole (for agar well diffusion method) at the center of the inhibition circle to the outer periphery of the inhibition circle at the longest observed radius of the inhibition circle.
  • the distance was determined by measuring the distance with a ruler. If a double inhibition zone was seen, the inner inhibition circle was measured. The results are shown in Table 3. In Table 3, "no activity" indicates that no inhibition circle was visually observed.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Virology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Agronomy & Crop Science (AREA)
  • Dentistry (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
PCT/JP2023/005404 2022-03-30 2023-02-16 新規な抗真菌剤 Ceased WO2023188945A1 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CN202380010874.2A CN117157408A (zh) 2022-03-30 2023-02-16 新型的抗真菌剂
EP23778975.5A EP4310190A4 (en) 2022-03-30 2023-02-16 Novel antifungal agent
JP2023530585A JP7568100B2 (ja) 2022-03-30 2023-02-16 新規な抗真菌剤
US18/505,399 US20240081339A1 (en) 2022-03-30 2023-11-09 Antifungal agent

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2022-055718 2022-03-30
JP2022055718A JP7279832B1 (ja) 2022-03-30 2022-03-30 新規な抗真菌物質

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US18/505,399 Continuation US20240081339A1 (en) 2022-03-30 2023-11-09 Antifungal agent

Publications (1)

Publication Number Publication Date
WO2023188945A1 true WO2023188945A1 (ja) 2023-10-05

Family

ID=86395862

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2023/005404 Ceased WO2023188945A1 (ja) 2022-03-30 2023-02-16 新規な抗真菌剤

Country Status (5)

Country Link
US (1) US20240081339A1 (https=)
EP (1) EP4310190A4 (https=)
JP (2) JP7279832B1 (https=)
CN (1) CN117157408A (https=)
WO (1) WO2023188945A1 (https=)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN120988855B (zh) * 2025-10-22 2026-04-17 聊城大学 一株球毛壳菌(Chaetomium globosum)5141-4、菌剂及应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040862A1 (en) * 1995-06-07 1996-12-19 Mount Sinai School Of Medicine Of The City University Of New York Antifungal compound produced by bacillus bacteria

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019", J NAT PROD, vol. 83, no. 3, 27 March 2020 (2020-03-27), pages 770 - 803
CRITS-CHRISTOPH ALEXANDER; DIAMOND SPENCER; BUTTERFIELD CRISTINA N.; THOMAS BRIAN C.; BANFIELD JILLIAN F.: "Novel soil bacteria possess diverse genes for secondary metabolite biosynthesis", CLEO: APPLICATIONS AND TECHNOLOGY 2019 SAN JOSE, CALIFORNIA UNITED STATES 5–10 MAY 2019, OPTICA, vol. 558, no. 7710, 13 June 2018 (2018-06-13), pages 440 - 444, XP036530492, DOI: 10.1038/s41586-018-0207-y *
JIANG YA-WEN, WANG JIA, CHEN MEI-HONG, LV YING-YING, QIU LI-HONG: "Acidipila dinghuensis sp. nov., an acidobacterium isolated from forest soil", INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY, SOCIETY FOR GENERAL MICROBIOLOGY, GB, vol. 66, no. 1, 1 January 2016 (2016-01-01), GB , pages 76 - 83, XP093094367, ISSN: 1466-5026, DOI: 10.1099/ijsem.0.000676 *
NEWMAN DAVID J., CRAGG GORDON M.: "Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019", JOURNAL OF NATURAL PRODUCTS, AMERICAN CHEMICAL SOCIETY, US, vol. 83, no. 3, 27 March 2020 (2020-03-27), US , pages 770 - 803, XP093094369, ISSN: 0163-3864, DOI: 10.1021/acs.jnatprod.9b01285 *
OKAMURA KEIKO, KAWAI AKIKO, YAMADA TAKESHI, HIRAISHI AKIRA: "Acidipila rosea gen. nov., sp. nov., an acidophilic chemoorganotrophic bacterium belonging to the phylum Acidobacteria : Acidipila rosea gen. nov., sp. nov.", FEMS MICROBIOLOGY LETTERS, NO LONGER PUBLISHED BY ELSEVIER, vol. 317, no. 2, 1 April 2011 (2011-04-01), pages 138 - 142, XP093094365, ISSN: 0378-1097, DOI: 10.1111/j.1574-6968.2011.02224.x *
See also references of EP4310190A4

Also Published As

Publication number Publication date
US20240081339A1 (en) 2024-03-14
JP2023147931A (ja) 2023-10-13
EP4310190A4 (en) 2025-04-23
CN117157408A (zh) 2023-12-01
JPWO2023188945A1 (https=) 2023-10-05
JP7279832B1 (ja) 2023-05-23
JP7568100B2 (ja) 2024-10-16
EP4310190A1 (en) 2024-01-24

Similar Documents

Publication Publication Date Title
Digra et al. An insight into endophytic antimicrobial compounds: an updated analysis
Abdalla et al. Endophytes as producers of peptides: an overview about the recently discovered peptides from endophytic microbes
Chen et al. Discovery of Niphimycin C from Streptomyces yongxingensis sp. nov. as a promising agrochemical fungicide for controlling banana fusarium wilt by destroying the mitochondrial structure and function
Chen et al. Calcineurin controls hyphal growth, virulence, and drug tolerance of Candida tropicalis
Kuo et al. Isolation of endophytic fungi with antimicrobial activity from medicinal plant Zanthoxylum simulans Hance
Pan et al. Endophytic fungus strain 28 isolated from Houttuynia cordata possesses wide-spectrum antifungal activity
Upadhyay et al. Production of ganoderic acid by Ganoderma lucidum RCKB-2010 and its therapeutic potential
Mathivanan et al. The effect of fungal secondary metabolites on bacterial and fungal pathogens
Barber et al. Small molecule natural products in human nasal/oral microbiota
Singh et al. Molecular identification of endophytic fungi isolated from medicinal plant
Ratnaweera et al. Antimicrobial constituents of Hypocrea virens, an endophyte of the mangrove-associate plant Premna serratifolia L.
JP7568100B2 (ja) 新規な抗真菌剤
Banerjee et al. The lipopeptides fengycin and iturin are involved in the anticandidal activity of endophytic Bacillus sp. as determined by experimental and in silico analysis
US20110002891A1 (en) Probiotic compositions and process thereof
Katif et al. Isolation and structure elucidation of desferrioxamine B and the new desferrioxamine B2 antibiotics from a brown marine macroalga Carpodesmia Tamariscifolia associated Streptomyces isolate
Barik et al. Phylogenetic placement of an endophytic fungus Fusarium oxysporum isolated from Acorus calamus rhizomes with antimicrobial activity
JP5907655B2 (ja) 食品保存料、カビ及び／又は酵母の増殖を阻害する方法、酵母及び／又は細菌の生育を阻害する方法
CN106946955A (zh) 真菌三糖酯化合物及其在制备防治植物真菌病害药物中的应用
Tran et al. Identification and bioactive properties of endophytic fungi isolated from phyllodes of Acacia species
Sudha et al. Volatile organic compounds of some antagonists against Lasiodiplodia theobromae, a pathogen of coconut.
JP6842088B2 (ja) 抗真菌活性を有する組成物
CN116077488B (zh) 雌马酚在防治病原真菌和细菌感染中的医药新应用
Abu-Mejdad et al. Isolation and molecular identification of yeasts, study their potential for producing killer toxins and evaluation of toxins activity against some bacteria and pathogenic fungi
CN108130278A (zh) 马齿苋菌核青霉及其在制备抗青枯菌药物中的应用
Wang et al. Discovery of (+)-Methyl Nonactate as a Potential Fungicide against Gummy Stem Blight

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 2023530585

Country of ref document: JP

WWE Wipo information: entry into national phase

Ref document number: 2023778975

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2023778975

Country of ref document: EP

Effective date: 20231018

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23778975

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE