P-77 緑膿菌由来テトラミン酸誘導体のClostridium difficileに対する抗菌作用(ポスター発表の部)

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Accumulating data suggest that quorum-sensing system possesses a variety of roles in pathogenesis of infections. Recent progress of this field demonstrated that Pseudomonas aeruginosa autoinducers may have bactericidal activity to certain bacterium, although the understanding of the spectrum of activity and the mechanisms of action is limited. The present study examined potential of bactericidal activity of the autoinducers and their degradation product tetramic acids against Clostridium difficile, an anerobic gram-positive bacterium and a cause of antibiotic-associated pseudomembrane colitis. Methods: P aeruginosa autoinducers and a panel of tetramic acid derivatives were chemically synthesized. Clinical isolates of C. difficile were incubated in broth under anerobic condition in the presence of the above compounds. The structure-activity correlation and the mechanisms of action were examined in several ways, such as time-kill assay and observation of changes of morphology by electron microscopy. Results: Some tetramic acid induced more than 3 log reduction of viability of C. difficile within 30min at a concentration of 50μM. The cell surface was suggested to be one of the targets for bactericidal activity of tetramic acid, because the disturbance of cell membrane was demonstrated by electron microscopy after exposure to tetramic acid. It is likely that enol structure of tetramic acid may be essential for antibacterial activity of this molecule. Interestingly, the simultaneous presence of tetramic acid at sub-MIC dramatically reduced the MICs of aminoglycoside amikacin against C. difficile from >256μg/ml to 0.5μg/ml. Conclusions: These results demonstrate potential of P. aeruginosa autoinducer-derived tetramic acids as a novel antimicrobial agent against C. difficile.
天然有機化合物討論会の論文
2008-09-01

P-77 緑膿菌由来テトラミン酸誘導体のClostridium difficileに対する抗菌作用(ポスター発表の部)

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