| Project/Area Number |
18580081
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | Osaka City University |
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Principal Investigator |
FUJITA Ken-ichi Osaka City University, Graduate School of Science, Associate professor (10285281)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Toshio Osaka City University, Graduate School of Science, Associate professor (10137185)
USUKI Yoshinosuke Osaka City University, Graduate School of Science, Associate Lecturer (30244651)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,860,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2006: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | fungi / Aspergillus nidulans / Candida albicans / cytoskeleton / microtubule / tubulin / antifungal antibiotics / dimorphic fungi / チュープリン / 二形性酵母 / 出芽酵母 / 儀菌糸形成 |
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| Research Abstract |
L-2,5-Dihydrophenylalanine (DHPA) shows the growth inhibition of Aspergillus spp. accompanying with morphological alterations. DHPA also induces the disappearance of microtubules and loss of the cytoplasmic pools of their monomeric α- and β-tubulins. DHPA was found to induce over-expression of all tubulin genes. In the DHPA-treated hyphae, ubiquitinated tubulins were not detected and cell free extracts from the hyphae did not accelerate the degradation of tubulins. These results suggest that DHPA unexpectedly facilitates the expression of tubulin genes.
We also investigated the effect of DHPA on a dimorphic fungus Candida albicans. DHPA inhibited the hyphal growth under a hyphal inducible condition and then induced yeast cells. In addition, the half of the yeast cells had swollen nuclei and cells were also observed without apparent actin patch. On the other hand, DHPA reduecd the pools of actin, tubulin, and ubiquitin. These results indicate that the action of DHPA on C. albicans would be different from that on Aspergillus spp.
Furthermore, we have searched drugs reducing tubulin pools against a budding yeast Saccharomyces cerevisiae. Isoamyl alcohol (IAA) was found to show such effects. IAA induced pseudohyphae accompanying with relative loss of a- and β-tubulins. Although decrease in tubulins was observed, spindle microtubule did not disappear apparently, and the distribution of chromosome seemed to proceed normally. However the delay of the distribution into daughter cells occurred. Moreover we found that decrease in tubulins was not due to the blockade of tubulin gene transcription and acceleration of tubulin degradation but the restriction of tubulin translation.
Together with results obtained above, we concluded that drug-induced tubulin loss was found in at least three genuses of fungi and the loss seemed to be involved in morphological changes. However we did not find common mechanisms among such phenomena.
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