We are engaged in activities to preserve useful fungal strain resources and provide them to universities, hospitals, research institutes, etc.

After joining the Japan Microbial Strain Conservation Federation (currently the Japan Society for Microbial Resources Conservation) in 1984, this center preserves useful fungal strain resources, centering on clinical isolates of pathogenic fungal species isolated at medical sites in Japan. We have been working on it for many years (TIMM Collection).

As of April 2010, we have about 9,700 fungal strains (yeast: about 6,500 strains, filamentous fungi: about 3,200 strains, etc.). As a result of the conclusion of the Convention on Biological Diversity in 1992, it has become difficult to obtain pathogenic microorganisms themselves and DNA as research samples from overseas. Therefore, the TIMM collection, which is dominated by clinically isolated strains isolated in Japan, will be a valuable bioresource for taking measures against fungal diseases in Japan.
We provide these preserved fungal strains to universities, hospitals, public research institutes, corporate research institutes, etc. that meet the standards for handling pathogenic fungi, and provide people who study and educate fungal diseases and pathogenic fungi. I am supporting. Through such activities, we will contribute to the health and security of people by making it possible to overcome fungal diseases and control infectious diseases.

　

We have been energetically working on basic and applied research on antifungal drugs as an important theme.

Preclinical research on antifungal drugs has maintained a global level as Japan's only specialized research institute and has earned high trust. We also provide data for the development of new antifungal drugs.

List of fungal strains stored frozen in an ultra-low temperature freezer (-80 ° C) stored in a storage room for antifungal drugs on the market.

■ External antifungal drug

■ Internal antifungal drug

We have developed various rapid and reliable genetic diagnostic methods.

In addition to developing various genetic diagnostic methods and putting them into practical use, we are also conducting joint research with the Japan Aerospace Exploration Agency (JAXA) in collaboration with the space environmental medicine research at Teikyo University Graduate School.

a: Taphrinomycotina b: Saccharomycotina c: Ascomycotina d: Kurobo fungi
e: Rust class f: Kinjin class g: Zygomycetes i: Entomovtra eyes ii: Mucol eyes

It is not uncommon for pathogenic fungi obtained from clinical specimens and their cultures to be difficult to identify morphologically. In general, fungi obtained from clinical materials lack phenotypic traits specific to the bacterial species, and often take various growth forms depending on the environment in which they are placed and various factors. The most reliable way to identify the causative organism necessary for the prevention, diagnosis, and treatment of deep-seated and superficial fungal diseases is to analyze the DNA sequence.

Many of the diagnostic methods we have developed have already been put into practical use, and it is possible to reliably identify bacterial species that are difficult to identify by phenotypes such as culture morphology and sugar assimilation.
In addition, by devising an analysis method for a wide range of fungi based on a database of fungal DNA as well as clinical materials, it has become possible to smoothly discover and phylogenetically classify new types of fungi. Based on these pioneering research results, pathological analysis of new pathogenic fungi in humans and animals that could not be sufficiently identified and diagnosed is being promoted.
Currently, at the request of medical institutions and research institutes in Japan and overseas, we are cooperating in advice on fungal research, joint research, and description of new species. For fungal infections in animals other than humans, especially rare animals, we cooperate with zoos in Japan and overseas to analyze the flora and provide information on infection prevention, diagnosis, and treatment.
We are also conducting research on the dynamics of fungi in special environments such as confined spaces. We are currently collaborating with the Institute of Space and Environmental Medicine, Teikyo University Graduate School, to analyze the fungal flora of the International Space Station and the Antarctic base, and to evaluate and address the risk of health problems as a joint research with the Japan Aerospace Exploration Agency (JAXA). I am doing research on.

We are conducting various studies such as fungal morphology, analysis of microstructure and function, gene expression, localization of biopolymers, determination of cell life and death, and infectious pathology.

Various optical microscopes such as transmission electron microscope (Hitachi H-7000), scanning electron microscope (JSM-7500F), fluorescence microscope, and differential interference contrast microscope are installed in this center.

Visualization techniques using these microscopes are used in various studies such as fungal morphology, microstructure and function analysis, gene expression, biopolymer localization, cell life / death determination, and infectious pathology. In particular, analysis of the mechanism of action of new antifungal drugs using an electron microscope is one of the main research themes at this center. In recent years, in addition to most of the external preparations marketed in the past, we have micromorphologically elucidated the mechanism of action of the deep-seated fungal disease therapeutic agents michaphangin, voriconazole, and amphotericin B lipid preparations on fungal cells.

Current main research themes include microstructure and functional analysis of pathogenic fungi, analysis of the mechanism of action of antifungal drugs and various antifungal substances, and pathological analysis of fungal infections using animal models.

Using dermatophytes (ringworm) as a model organism, we are analyzing the protein and gene level of the infection mechanism of the causative fungus.

At this center, we are conducting protein and gene level analysis on the infection mechanism of the causative organism in order to take effective control against fungal diseases.

The main target of analysis is dermatophytes (ringworm). Ringworm (athlete's foot, ringworm, ringworm) is said to be the oldest infectious disease in humankind. The estimated number of ringworm cases in Japan exceeds 20 million, and it is estimated that more than 10% of the population is constantly affected in almost all regions of the world. At the same time as establishing a gene manipulation system (gene transfer, gene overexpression, gene knockout, etc.) in order to clarify the infection mechanism of ringworm, which is the causative agent of tinea corporis, which can be said to be a global infectious disease, at the molecular level. , Established models of tinea corporis and tinea pedis using guinea pigs. Using these experimental systems, we are proceeding with the analysis of pathogenic factors, focusing on the secretory protease with keratin-degrading activity, that is, "keratinase", whose essentiality in the infectious process of this bacterium has been pointed out for a long time. ..

Ringworm M into which the Green fluorescent protein (eGFP) gene has been introduced

Phenotypic analysis of Trichophyton disrupting transcription factors involved in secretory protease gene expression

 

The focus is not only on the analysis of the mechanism, but also on research that leads to the prevention and treatment of fungal diseases.

The focus is not only on the analysis of the mechanism, but also on research that leads to the prevention and treatment of fungal diseases. We are also researching fungal components as immunomodulators.

The interaction between the fungus and the host shows a complicated aspect including the interaction with other microorganisms in the host, and it is necessary to understand it for the development of new preventive treatment methods. From this point of view, we are conducting research on themes such as biological defense against fungal infections, regulation of biological immunocompetence by fungal infections or fungal components, and infection control by natural products.
As a study of the biological defense ability against fungal infections, we are investigating the ability of various leukocytes to inhibit the growth of Candida albicans, and have clarified the effects of Chinese herbal supplements, enhancement of activity by natural products, and infection prevention and treatment effects in infection models. In addition, since the fungal component itself including polysaccharides stimulates and affects the immune system, we are also researching the fungal component as an immunomodulator.
We are also searching for bioactive substances and virulence factors produced by fungi, and analyzing the mechanism of morphogenesis of dimorphic development such as C. albicans and its control. Recent research has shown that C. albicans-produced yeast-type growth-promoting substance (terpenoid known as quorum sensing substance) farnesol does not merely act as a pathogen, but prevents the aggravation of mucosal infections. Revealed.

Developing cures for fungal diseases

With the goal of reducing the number of ringworm patients, who account for more than 10% of the population, we are energetically conducting research on new foot bath therapies and gas treatments.

We are developing treatments for fungal diseases with new strategies that are difficult for ordinary pharmaceutical companies to implement. As a field of chemotherapy, we are investigating the treatment of candidiasis and ringworm using small molecule and volatile plant essential oils. It is a therapy that takes advantage of the characteristics (safety, antibacterial activity, permeability, volatility, anti-inflammatory effect) of plant essential oils and natural food ingredients. With the goal of reducing the number of ringworm patients, who account for more than 10% of the population, we are energetically conducting research on new foot bath therapies and gas treatments. In foot bath therapy, clinical research has progressed and it has been clarified that a hot foot bath containing essential oils is effective. In addition, as a gas therapy, we are trying to develop a new treatment method for ringworm as a drug delivery by putting an insole soaked in essential oil and putting on shoes.

We are also conducting research on the preventive and therapeutic effects of plant essential oils and natural food ingredients on oral candidiasis and vaginal candidiasis. Since the causative bacterium, Candida yeast, exists as a normal microbial flora, it is assumed that it is impossible to completely eliminate the bacterium from the skin and mucous membranes, and it is said that these yeasts will create a situation where they cannot exert pathogenicity with natural products. It's a strategy.

We are conducting research and development that is useful for the prevention (treatment) of fungal diseases.

In the future, I would like to further study the possibility that indigenous human bacteria control fungal diseases by interacting with fungi.

As a preventive (treatment) study of oral candidiasis, we conducted research on lactic acid bacteria that directly interact with the causative bacterium Candida albicans. As a result, some lactic acid bacteria can suppress the onset of oral candidiasis by directly adhering to C. albicans, thereby inhibiting the attachment of C. albicans to the oral tissues and the growth of hyphal forms. I found out. (See photo) This research result is an example of the antifungal activity of lactic acid bacteria as a probiotic.

Fluorescence microscope images of Candida bacteria that have grown hyphal and lactic acid bacteria that have adhered to Candida bacteria

Trial sale of "UHA Sita Clear" "UHA Sita Clear" is a delicious non-sugar candy containing DOMAC, an aroma component complex that is a unique ingredient that reduces oral candidiasis. In the limited trial sale, it is announced on TV commercials, JR Tokai trains, hanging advertisements, large wall posters of SHIZUOKA109, cityscape, etc., and it also has an aspect of oral care awareness raising activities.

We sold "UHA Sita Clear"

Developed a delicious non-sugar candy containing DOMAC, an aroma component complex that is a unique ingredient that reduces candida in the mouth. In the limited trial sale, it was announced on TV commercials, JR Central trains, hanging advertisements, large wall posters of SHIZUOKA109, cityscapes, etc., and contributed to awareness raising activities for oral care.

UHA Mikakuto "UHA Sita Clear" special site