| Summary: | 碩士 === 高雄醫學大學 === 醫學檢驗生物技術學研究所 === 102 === Staphylococcus aureus is a gram-positive coccal bacterium that cause nosocomial infections in human and animals.It can cause a range of mild to severe infections such as endocarditis, septicemia, and osteomyelitis. In recent years, the global warning of nosocomial infection methicillin-resistant Staphylococcus aureus (MRSA) which is increasingly difficult to manage. It is worth noting that vancomycin resistant have been reported around the world. Therefore, the development of new drugs is an urgent matter. In this study, six potential compounds, which were selected from 108 small compounds, revealed their bactericidal effect against MRSA and multi-drug resisant clinical isolates. Toxicity testing via the normal cell lines (HEK-293 and chang cell) with IC50 values of six compounds are 33.17, 43.10, 35.2, 44.27,> 50, 28.35 μg / ml, respectively. These concentrations were higher than bactericidal concentration (10 μg / ml). Although these six small molecule compounds are modified from quinolone, these compounds still had bactericidal effect against quinolone-resistant strains with gyrA, grlA mutations and efflux pump activity.Synergist effect of NO.17 compound and oxacillin was found in multi-drug resistant clinical isolates and reduced the oxacillin the oxacillin concentration.Quantitative real time PCR demonstrated that NO.17 compound could down-regulate the expression of mecA with or without oxacillin.SEM and TEM found NO.17 compound could caused DNA condensation and cell wall destruct.These results indicated that NO.17 compound could be a potential lead compound for evolveing the more efficient structure in the future.
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