Our lab. are dealing with bio-active substances that affect various physiological functions such as cell growth, cell death, immunity, and aging. Among them, we are especially focusing the substances restrict drug-resistance. The development of antifungal antibiotics with novel modes of action and fewer adverse effects in humans is urgently required because of an increase in opportunistic fungal infections in immunocompromised patients and the elderly. As current antifungal targets are limited to the functions and structures unique to fungi, namely ergosterol, the cell wall, and cytosine deaminase, it has been difficult to develop novel antibiotics. In addition, clinical isolates have been reported to show resistance to these antifungals. Therefore, strategies for overcoming drug-resistance should be developed to improve antifungal chemotherapy. We are exploring bio-active substances derived from natural resources that restrict the fungal drug-resistance thereby restoring the weakened antifungal activity because of drug resistance. Moreover, we are also investigating the innate mechanism expressing drug-resistance by using the substances.

　We have been working in the field of toxin-antitoxin (TA) systems in Escherichia coli. Each TA system is encoded by two small genes, which usually overlap by a few bases. A toxin and its cognate antitoxin form a stable TA complex, which blocks the function of the toxin. Almost all bacteria contain a number of TA systems, targeting various cellular functions from DNA replication, mRNA stability, protein synthesis and cell wall biosynthesis to regulate cell growth and death. As the antitoxin is less stable than the toxin in the cell, it has to be constantly produced to inhibit the toxin. Under stress conditions, antitoxins are digested by stress-induced proteases to release free toxins, resulting in cell growth arrest and eventual cell death. A number of TA systems appear to be related to the pathogenicity of a bacterium. The TA systems in M. tuberculosis may play important roles in the maintenance of the extremely long dormancy of this pathogen inside macrophage. On the basis of this idea, it is perhaps surprising that E. coli also contains comparatively a large number of TA systems. We are studying to understand the physiological functions of TA systems in bacteria.