緑膿菌Quorum sensing機構と抗菌薬抵抗性について

The opportunistic pathogen Pseudomonas aeruginosa causes immunocompromised individuals and patients with cystic fibrosis to serious nosocomial infections. Although we choose the most suitable antibiotics on the basis of minimum inhibitory concentration (MIC), it is often difficult to eradicate pathogen. This phenomenon is called antibiotic tolerance, which is different from antibiotic resistance. Antibiotic tolerance is the ability of bacteria to survive but not grow in the presence of antibiotics. To understand the mechanism of antibiotic tolerance, we investigated the relation of quorum sensing system and antibiotic tolerance. With 4 x MIC or 8 x MIC of ofloxacin, the lasR mutant and the lasI mutant were killed more rapidly than the parental strain, but the survival rates of the rhlR mutant and the rhlI mutant were the same level of the parental strain. And with 8 x MIC of ofloxacin, the lasR-rhlR double knockout mutant and the lasI-rhlI double knockout mutant were killed more rapidly than the parental strain. To investigate these phenomena more detail, we measured the promoter activities of lasR and rhlR genes. The promoter activity of the lasR was induced with ofloxacin in the logarithmic and the stationary phase cells, but the promoter activity of the rhlR was not. Continuously, we measured the expression levels of lasR, lasI, rhlR, and rhlI. The expression of the lasR was induced with lower concentration of ofloxacin, but higher concentration of ofloxacin repressed expression of the lasR. And expression of lasI, rhlR and rhlI genes were repressed or irrelevant to the concentration of ofloxacin. In conclusion, we revealed that the las quorum sensing system was related to the antibiotic tolerance, and the antibiotic tolerance was promoted by the las quorum sensing system.

公開日:2010年1月24日で登録したコンテンツは、国立情報学研究所において電子化したものです。