SHIMIZU Tohru INSTITUTE OF BASIC MEDICAL SCIENCES, UNIVERSITY OF TSUKUBA, ASSOCIATE PROFESSOR, 基礎医学系, 助教授 (80235655)
OHTA Toshiko MEDICAL TECHNOLOGY, UNIVERSITY OF TSUKUBA, PROFESSOR, 医療短期大学, 教授 (40233134)
NAKAMURA Shinichi DEPARTMENT OF MICROBIOLOGY, KANAZAWA UNIVERSITY, PROFESSOR, 医学部, 教授 (90019620)
KURAZONO Hisao HEALTH SCIENCES, OKAYAMA UNIVERSITY, PROFESSOR, 医学部, 教授 (90186487)
|Budget Amount *help
¥36,500,000 (Direct Cost : ¥36,500,000)
Fiscal Year 1999 : ¥8,000,000 (Direct Cost : ¥8,000,000)
Fiscal Year 1998 : ¥8,200,000 (Direct Cost : ¥8,200,000)
Fiscal Year 1997 : ¥8,800,000 (Direct Cost : ¥8,800,000)
Fiscal Year 1996 : ¥11,500,000 (Direct Cost : ¥11,500,000)
Molecular mechanism of production of toxins and the other virulence factors in Gram positive bacteria has been investigated to develop novel infection control measures for Gram positive bacteria which produce variety of virulence factors to cause desease in human.
1. The production of toxins and enzymes was regulated by the environmental factors.
The production of toxins (α, β, γ, ε, θ, etc, in Clostridium perfringens, toxin A and B in C. difficile, soluble and surface virulent factors in Staphylococcus aureus) was regulated by the growth phase, density/population of bacteria (quoram sensing), carbon source and nutritional substrate, inter-cellular factors (like pheromon). Under the stressful condition for bacteria, ie ; heat, extream pH, in the presence of heavy metals, antibiotics, the bacteria induced the stress responsible genes including virulent genes.
2. Specific receptors for sensing environmental factors.
Each bacterium has a certain specific receptors for environmental factors, i
.e., the most common one is the sensor component of two-component system. In C. perfringens, several systems have been identified, among which one for activation and the other for inhibition of production of toxin. In S. aureus, the receptors for zinc, alkaline, β-lactams were mostly identified.
3. Information transmitting network in bacteria.
Along with genomic analysis of C. perfringens, and that of Staphylococci, molecular basis of information transmitting system in bacteria has been made clear from receptor to effecter production as an sequential "molecular net work" with global regulatory system. This information is useful for the design of antibiotics in future.
4. Regulation at the level of transcription, translation, post translation and secretion from cell.
On basing upon those results, molecular net work of virulent factor production has been more clearly confirmed and the results will contribute to those who are looking for more specific effective anti-infection drugs and preventive measures. Less