P-19 病原性真菌Candida albicansのクオラムセンシング物質(ポスター発表の部)

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The human fungal pathogen Candida albicans is harmless under normal conditions. However, for the patient whose immunity is decreased, it causes an opportunistic infection and shows serious symptoms. C. albicans exhibits various phenomena according to its cell density: initiation of cell proliferation, morphological change, and expression of pathogenicity. It is thought that these responses are controlled by a quorum sensing system that can sense the cell density. Quorum sensing compounds and mechanisms in bacteria are well known. However, fungal quorum sensing molecules are not well studied compared to that of bacteria (Figure 1). It is already known that the medium from a high density culture can reduce the lag time prior to exponential cell growth. It is thought that conditioned media contain a quorum sensing compound that has a role in cell growth initiation. In this study, we constructed a quorum sensing assay system, isolated the active compound, and determined the structure of it, as well as analyzed the activity of this compound using a growth assay and a whole genome microarray of C. albicans. Concentrated medium of C. albicans was fractionated by several steps of chromatography guided by lag time shortening activity, then finally purified by reversed phase HPLC as a single compound. The structure of the purified quorum sensing compound was determined from spectral data including NMR, MS, and UV as 2-(4-hydroxyphenyl)ethanol (tyrosol). Synthetic tyrosol had identical spectral data and it also exhibited similar activity as natural tyrosol (Figure 3). Tyrosol also accelerates the morphological conversion of C. albicans cells from the yeast form to the filamentous form, which is known as germ tube formation. This suggests that tyrosol has a role not only in cell growth but also in expression of pathogenicity (Figure 4). The biological activity was analyzed using a C. albicans whole genome microarray. The expression level of several genes involved in DNA replication and cell division as well as some genes involved in germ tube formation were enhanced by the addition of tyrosol (Figure 5).
天然有機化合物討論会の論文
2005-09-15

P-19 病原性真菌Candida albicansのクオラムセンシング物質(ポスター発表の部)

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