| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Outline of Final Research Achievements |
Macrolides have been reported to exert a variety of effects on both host immunomodulation as well as repression of bacterial pathogenicity. In this study, we report that the 3′,5′-cyclic diguanylic acid (c-di-GMP) signaling system, which regulates virulence to the host, was affected by the macrolide azithromycin (AZM). Using DNA microarray analysis, we selected two Pseudomonas aeruginosa genes related to c-di-GMP metabolism that were significantly affected by AZM treatment. The expression of these genes was significantly repressed by AZM in a time- and dose-dependent manner, whereas no difference in pde gene expression was observed in the absence of AZM. In-frame deletion of the pde gene affected both virulence factors and the quorum-sensing system and significantly decreased total bacteria in a mouse pneumonia model compared to the wild-type strain. These results suggest that macrolides affect virulence factor production via the c-di-GMP regulatory system.
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