Diaz Dilernia Fernando, Watson David, Heinrichs David E, Vasarhelyi Edward
Adult Hip and Knee Reconstructive Surgery, London Health Sciences Centre, Division of Orthopedic Surgery, Department of Surgery, Schulich School of Medicine & Dentistry, Western University, London, Canada.
Division of Orthopedic Surgery, Department of Surgery, Kingston Health Sciences Center, Queen's University, Kingston, Canada.
Bone Joint Res. 2024 Nov 7;13(11):632-646. doi: 10.1302/2046-3758.1311.BJR-2024-0148.R1.
The mechanism by which synovial fluid (SF) kills bacteria has not yet been elucidated, and a better understanding is needed. We sought to analyze the antimicrobial properties of exogenous copper in human SF against .
We performed in vitro growth and viability assays to determine the capability of to survive in SF with the addition of 10 µM of copper. We determined the minimum bactericidal concentration of copper (MBC-Cu) and evaluated its sensitivity to killing, comparing wild type (WT) and CopAZB-deficient USA300 strains.
UAMS-1 demonstrated a greater sensitivity to SF compared to USA300 WT at 12 hours (p = 0.001) and 24 hours (p = 0.027). UAMS-1 died in statistically significant quantities at 24 hours (p = 0.017), and USA300 WT survived at 24 hours. UAMS-1 was more susceptible to the addition of copper at four (p = 0.001), 12 (p = 0.005), and 24 hours (p = 0.006). We confirmed a high sensitivity to killing with the addition of exogenous copper on both strains at four (p = 0.011), 12 (p = 0.011), and 24 hours (p = 0.011). WT and CopAZB-deficient USA300 strains significantly died in SF, demonstrating a MBC-Cu of 50 µM against USA300 WT (p = 0.011).
SF has antimicrobial properties against , and UAMS-1 was more sensitive than USA300 WT. Adding 10 µM of copper was highly toxic, confirming its bactericidal effect. We found CopAZB proteins to be involved in copper effluxion by demonstrating the high sensitivity of mutant strains to lower copper concentrations. Thus, we propose CopAZB proteins as potential targets and use exogenous copper as a treatment alternative against .
滑液（SF）杀灭细菌的机制尚未阐明，需要更深入的了解。我们试图分析外源性铜在人滑液中对……的抗菌特性。
我们进行了体外生长和活力测定，以确定……在添加10 μM铜的滑液中的存活能力。我们确定了铜的最低杀菌浓度（MBC-Cu），并比较野生型（WT）和CopAZB缺陷型USA300菌株对其杀伤的敏感性。
在12小时（p = 0.001）和24小时（p = 0.027）时，UAMS-1比USA300 WT对滑液表现出更高的敏感性。UAMS-1在24小时时大量死亡（p = 0.017），而USA300 WT在24小时时存活。在4小时（p = 0.001）、12小时（p = 0.005）和24小时（p = 0.006）时，UAMS-1对外源性铜的添加更敏感。我们证实在4小时（p = 0.011）、12小时（p = 0.011）和24小时（p = 0.011）时，两种菌株添加外源性铜后对杀伤均高度敏感。WT和CopAZB缺陷型USA300菌株在滑液中显著死亡，显示对USA300 WT的MBC-Cu为50 μM（p = 0.011）。
滑液对……具有抗菌特性，且UAMS-1比USA300 WT更敏感。添加10 μM铜具有高度毒性，证实了其杀菌作用。通过证明突变菌株对较低铜浓度的高度敏感性，我们发现CopAZB蛋白参与铜外排。因此，我们提出将CopAZB蛋白作为潜在靶点，并使用外源性铜作为对抗……的治疗选择。
