|Budget Amount *help
¥6,600,000 (Direct Cost : ¥6,600,000)
Fiscal Year 1997 : ¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1996 : ¥4,500,000 (Direct Cost : ¥4,500,000)
A lot of bacterial drug exporters have recently been found in pathogens confering the mutidrug resistance. The development of an inhibitor for these multidrug exporters are very useful for chemotherapy. In this study, we developed the system for screening inhibitors for bacterial drug exporters and checked more than hundred thousand compounds. At first, norA and mexA/B-expressing S.aureus and P.aeruginosa strains, respectively, were constructed using these gene-defective strains as host cells. The resistance levels of these exporter gene-expresssing strains and their control host strains against quinolone of beta-lactam antibiotics were systematically determined in the presence or absence of various screening compounds. As a result, some inhibitor candidates were found, however, the probability for the appearance of the inhibitors was unexpectedly low, indicating that it is difficult to overcome the bacterial multidrug resistance based on the multidrug exporters. Similar results were independently obtained by Microcide Co. in USA.In the separate experiments, we investigated the inhibitors for a tetracycline exporter, Tet(K), in S.Aureus. An indane derivative was revealed to be a Tet (K)-specific inhibitor.