Multifungin의 약제 내성 포도상구균에 의한 환기관 바이오필름에 대한 효과 = Effects of multifungin on tympanostomy tube biofilms from methicillin-resistant Staphylococcus aureus

다국어 초록 (Multilingual Abstract)

Effects of multifungin on tympanostomy tube biofilms from methicillin-resistant Staphylococcus aureus Eu-Ri Jo Advisor : Prof. Sung Il Cho, MD, PhD Department of Biomedical Sciences Graduate School of Chosun University Purpose: Biofilms formed by methicillin-resistant Staphylococcus aureus （MRSA） on tympanostomy tubes are known to be a major cause of refractory and persistent otorrhea. This study aimed to evaluate the in vitro antibacterial and antibiofilm effects of multifungin against MRSA. Methods: The antibacterial and antibiofilm effects of multifungin were evaluated using bacterial growth inhibition, adhesion, biofilm formation, and biofilm eradication assays. In addition, biofilm hydrolytic activity assays and wheat germ agglutinin （WGA） fluorescence analysis were performed to examine changes in the extracellular matrix. Furthermore, the effects of multifungin at various concentrations on MRSA biofilms formed on the surface of tympanostomy tubes were observed using scanning electron microscopy. Results: The minimum inhibitory concentration of multifungin against MRSA was 1.0 μM, indicating strong antibacterial activity. Multifungin inhibited MRSA biofilm formation and significantly reduced bacterial adhesion in a concentration-dependent manner. Treatment with multifungin increased the eradication of preformed mature MRSA biofilms. In addition, metabolic activity was reduced, as demonstrated by decreased fluorescein diacetate hydrolysis and ATP levels, and the residual biofilm biomass was significantly decreased. Moreover, the extracellular polymeric matrix of MRSA biofilms was effectively disrupted, as indicated by reduced WGA fluorescence intensity. Scanning electron microscopy analysis showed that MRSA biofilms and bacterial colonies on the surface of tympanostomy tubes were reduced in a concentration-dependent manner in the multifungin-treated groups. Conclusion: Multifungin exhibited strong antibacterial, antibiofilm, and biofilm-eradicating activities against MRSA. In particular, it showed effective inhibitory and eradication effects against biofilms formed on the surface of tympanostomy tubes. These findings suggest that multifungin may be a promising drug candidate for the treatment of refractory otorrhea associated with MRSA infection and biofilm formation. Keywords: Multifungin, Staphylococcus aureus, biofilm, otorrhea

목차 (Table of Contents)

• 1. 서 론 1
• 2. 재료 및 방법 3
• 2-1. 세균 균주, 배양 조건 및 약물 처리 3
• 2-2. 항균 활성 분석 3
• 2-3. 크리스탈 바이올렛 염색을 이용한 바이오필름 형성 및 제거 분석 4
• 2-4. 부착 분석 5
• 2-5. 바이오필름 가수분해 활성 분석 5
• 2-6. ATP 정량 분석 6
• 2-7. 최소 바이오필름 제거 농도(MBEC) 측정 6
• 2-8. MRSA 바이오필름 기질 관찰 7
• 2-9. 고막환기관 표면 MRSA 바이오필름의 주사전자현미경 분석 7
• 2-10. 통계 분석 8
• 3. 결 과 9
• 3-1. MRSA 성장, 바이오필름 형성 및 부착에 대한 multifungin 억제 활성 9
• 3-2. MRSA 바이오필름에 대한 multifungin의 제거 활성 9
• 3-3. MRSA 바이오필름 기질 및 고막 환기관 바이오필름에 대한 multifungin의 항바이오필름 활성 10
• 4. 토 론 11
• 5. 참고문헌 13