| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Treatment of Pseudomonas aeruginosa infection is full of difficulty due to drug resistance of the organism. However, the macrolide, which shows no antibacterial activity to P.aeruginosa, is effective for treatment of patients with chronic pseudomonal respiratory tract infection. We discovered that macrolide had bactericidal effect in stationary growth phase in P.aeruginosa. NPN, fluorescent probe, assay proved that azithromycin, a macrolide, interact to outermembrane of the organism. In addition, I found that the macrolide sensitivity depended on quorum sensing system (QS system) of P.aeruginosa and identified the gene, which was controlled by this QS system and was related to macrolide sensitivity. In result, expression of the pqsA-E operon, which was one of Pseudomonas qquinolone signal (PQS) biosynthesis genes, was required for macrolide susceptibility. Next, to clarify expression mechanism of the operon, we established a mutant that had insertion of pqsA'-lacZ fusion on it's chromosome and made a random transposon mutant library of the mutant. We identified 27 genes, which related pqsA-E operon expression. Genes related to flagellum, cell division, nucleotide biosynthesis, metabolism, drug and, PQS biosynthesis genes (pqsA, pqsB, pqsC, pqsD, pqsH, pqsR) were included. These results suggested that macrolide-susceptibility in stationary growth phase may required activation of those genes
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