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奎宁增强抗菌蓝光的杀菌效果:对治疗皮肤念珠菌病的启示。

Quinine Improves the Fungicidal Effects of Antimicrobial Blue Light: Implications for the Treatment of Cutaneous Candidiasis.

机构信息

Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

出版信息

Lasers Surg Med. 2020 Jul;52(6):569-575. doi: 10.1002/lsm.23180. Epub 2019 Nov 19.

Abstract

BACKGROUND AND OBJECTIVE

Candida albicans is an opportunistic fungal pathogen of clinical importance and is the primary cause of fungal-associated wound infections, sepsis, or pneumonia in immunocompromised individuals. With the rise in antimicrobial resistance, it is becoming increasingly difficult to successfully treat fungal infections using traditional antifungals, signifying that alternative non-traditional approaches must be explored for their efficacy.

STUDY DESIGN/MATERIALS AND METHODS: We investigated the combination of antimicrobial blue light (aBL) and quinine hydrochloride (Q-HCL) for improved inactivation of C. albicans, in vitro and in vivo, relative to either monotherapy. In addition, we evaluated the safety of this combination therapy in vivo using the TUNEL assay.

RESULTS

The combination of aBL (108 J/cm ) with Q-HCL (1 mg/mL) resulted in a significant improvement in the inactivation of C. albicans planktonic cells in vitro, where a 7.04 log colony forming units (CFU) reduction was achieved, compared with aBL alone that only inactivated 3.06 log CFU (P < 0.001) or Q-HCL alone which did not result in a loss of viability. aBL + Q-HCL was also effective at inactivating 48-hour biofilms, with an inactivation 1.73 log CFU at the dose of 108 J/cm aBL and 1 mg/mL Q-HCL, compared with only a 0.73 or 0.66 log CFU by aBL and Q-HCL alone, respectively (P < 0.001). Transmission electron microscopy revealed that aBL + Q-HCL induced morphological and ultrastructural changes consistent with cell wall and cytoplasmic damage. In addition, aBL + Q-HCL was effective at eliminating C. albicans within mouse abrasion wounds, with a 2.47 log relative luminescence unit (RLU) reduction at the dose of 324 J/cm aBL and 0.4 mg/cm Q-HCL, compared with a 1.44 log RLU reduction by aBL alone. Q-HCL or nystatin alone did not significantly reduce the RLU. The TUNEL assay revealed some apoptotic cells before and 24 hours following treatment with aBL + Q-HCL.

CONCLUSION

The combination of aBL + Q-HCL was effective at eliminating C. albicans both in vitro and in vivo. A comprehensive assessment of toxicity (cytotoxicity and genotoxicity) is required to fully determine the safety of aBL + Q-HCL therapy at different doses. In conclusion, the combination of aBL and Q-HCL may be a viable option for the treatment of cutaneous candidiasis. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

摘要

背景与目的

白色念珠菌是一种具有临床重要性的机会性真菌病原体,是免疫功能低下个体中真菌相关伤口感染、败血症或肺炎的主要原因。随着抗菌药物耐药性的增加,使用传统抗真菌药物成功治疗真菌感染变得越来越困难,这表明必须探索替代的非传统方法来提高其疗效。

研究设计/材料和方法:我们研究了抗菌蓝光(aBL)和盐酸奎宁(Q-HCL)联合使用对白色念珠菌的体外和体内灭活效果,与单药治疗相比。此外,我们还使用 TUNEL 检测法评估了这种联合治疗的体内安全性。

结果

aBL(108 J/cm )与 Q-HCL(1 mg/mL)联合使用可显著提高白色念珠菌浮游细胞的体外灭活效果,与单独使用 aBL 灭活 3.06 对数 CFU 相比,可使 7.04 对数 CFU 的减少(P < 0.001),或单独使用 Q-HCL 不导致活力丧失。aBL + Q-HCL 还能有效灭活 48 小时生物膜,在 108 J/cm aBL 和 1 mg/mL Q-HCL 的剂量下,灭活 1.73 对数 CFU,而单独使用 aBL 或 Q-HCL 分别为 0.73 或 0.66 对数 CFU(P < 0.001)。透射电子显微镜显示,aBL + Q-HCL 诱导了与细胞壁和细胞质损伤一致的形态和超微结构变化。此外,aBL + Q-HCL 能有效消除小鼠擦伤伤口中的白色念珠菌,在 324 J/cm aBL 和 0.4 mg/cm Q-HCL 的剂量下,相对发光单位(RLU)减少 2.47 对数,而单独使用 aBL 减少 1.44 对数 RLU。Q-HCL 或制霉菌素单独使用均不能显著减少 RLU。TUNEL 检测显示,在用 aBL + Q-HCL 处理前后 24 小时内,有一些凋亡细胞。

结论

aBL + Q-HCL 联合应用在体外和体内均能有效消除白色念珠菌。需要全面评估毒性(细胞毒性和遗传毒性),以确定不同剂量下 aBL + Q-HCL 治疗的安全性。总之,aBL 和 Q-HCL 的联合应用可能是治疗皮肤念珠菌病的一种可行选择。激光外科学杂志。© 2019 威利父子公司

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