2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/659615摘要：Methicillin抗藥金黃色葡萄球菌(methicillin-resistant Staphylococcus aureus，簡稱MRSA) 的增加為全球的問題，發展新藥物、新劑型或新抗菌方法為許多科學家努力的方向。MRSA不只是對methicillin抗藥，此類菌株對所有β-lactam類藥物均是抗藥，且經常對其他種類抗生素也常是多重抗藥(multidrug resistant)。由於抗生素極容易引發細菌的抗藥產生，而光動力殺菌則是被認為較不易引起抗性的產生，因此光動力殺菌已是許多學者發展抗微生物努力的目標。此整合型計劃總主持人陳老師團隊發現Compound X，簡稱CX（專利申請中，在本計畫中以CX代替）與hematoporphyrin (HP)光感物質對革蘭氏陽性細菌具有顯著協同加乘效果(synergistic effect)，但由於初步只先測試HP及少數菌株，對於其他光感物質或菌株的效果為何並不清楚，因此在此計畫中我們將選擇toluidine bluo O來測試CX是否也具加強效果。事實上，MRSA臨床菌株間的差異性相當大，光動力對不同菌株是否都具有相同效力不得而知。目前已知不同基因型的MRSA，對抗生素的感受性常有差異，如ST239:SCCmec type III對非β-lactam類較為抗藥，而ST59:SCCmec type IV對非β-lactam類較不抗藥。由於不同基因型代表不同生物型特性，有必要對不同的基因型MRSA分別測試。我們將於第一年針對不同基因型的MRSA臨床菌株(至少包括ST239:SCCmec type III、ST59:SCCmec type IV與ST59:SCCmec typeVT)來測試CX輔助光動力殺菌的效果，細菌培養以懸浮菌體為主，分析何種基因型可能與光動力殺菌感受性有關聯。但由於金黃色葡萄球菌是臨床上著名會產生生物膜的細菌之一，生物膜的形成會造成治療的問題。因此第二年則進一步測試CX輔助光動力對MRSA生物膜的殺菌效果。第三年則將進一步測試CX輔助光動力對MRSA對細菌產生毒素的影響，例如對hemolysin或Panton-Valentine leukocidin (PVL)等的影響。而若CX輔助光動力可降低金黃色葡萄球菌毒素的產生，則更適合未來在臨床上的應用。<br> Abstract: The increasing worldwide occurrence of antibiotic-resistant bacteria is a considerable concern. Methicillin-resistant Staphylococcus aureus (MRSA) infections have become a serious problem in many countries. MRSA strains are not just resistant to methicillin. They are resistant to all β-lactams and are usually resistant to other antibiotics (which means multidrug-resistant). Photodynamic inactivation is considered as a potential alternative for treatment of multidrug-resistant bacteria. Professor Chen CT, our collaborator, recently found that a compound X (CX, submitted to patent application) can enhance photodynamic bactericidal effect of hematoporphyrin (HP) on gram-positive bacteria. Since they only tested HP and few bacterial species, it is unknown whether CX can enhance the phototoxicity of other photosensitizers or not. In addition, different genotypes (SCCmec, multilocus sequence type) of MRSA strains usually have different resistance patterns and other characteristics and usually represent different clinical significance. For example, ST59:SCCmec type IV is relatively not resistant to non-β-lactams, while ST239:SCCmec type III is usually resistant to many non-β-lactams. In this three-year project, we would like to choose toluidine blue O (TBO) as photosensitizer to be combined with CX to test photodynamic bactericidal activity against different genotypes of MRSA. In the first year, we will determine the genotypes of MRSA isolates and test the efficacy of CX+TBO on planktonic cells of MRSA. In the second year, we will determine whether CX+TBO is active against MRSA biofilm. During the third year, we will investigate the effect of CX+TBO on expression of various toxin genes of MRSA including hemolysin and Panton-Valentine leukocidin, etc.Methicillin抗藥金黃葡萄球菌生物膜CX輔助光動力殺菌毒素Methicillin-resistant Staphylococcus aureusbiofilmCX enhanced photodynamic inactivationtoxin