Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, USA.
Photochem Photobiol. 2012 May-Jun;88(3):596-603. doi: 10.1111/j.1751-1097.2011.01039.x. Epub 2011 Dec 20.
Cutaneous and mucocutaneous Candida infections are considered to be important targets for antimicrobial photodynamic therapy (PDT). Clinical application of antimicrobial PDT will require strategies that enhance microbial killing while minimizing damage to host tissue. Increasing the sensitivity of infectious agents to PDT will help achieve this goal. Our previous studies demonstrated that raising the level of oxidative stress in Candida by interfering with fungal respiration increased the efficiency of PDT. Therefore, we sought to identify compounds in clinical use that would augment the oxidative stress caused by PDT by contributing to reactive oxygen species (ROS) formation themselves. Based on the ability of the antifungal miconazole to induce ROS in Candida, we tested several azole antifungals for their ability to augment PDT in vitro. Although miconazole and ketoconazole both stimulated ROS production in Candida albicans, only miconazole enhanced the killing of C. albicans and induced prolonged fungistasis in organisms that survived PDT using the porphyrin TMP-1363 and the phenothiazine methylene blue as photosensitizers. The data suggest that miconazole could be used to increase the efficacy of PDT against C. albicans, and its mechanism of action is likely to be multifactorial.
皮肤和黏膜念珠菌感染被认为是抗菌光动力疗法（PDT）的重要靶点。抗菌 PDT 的临床应用将需要增强微生物杀伤作用，同时最大限度地减少对宿主组织的损伤的策略。提高感染剂对 PDT 的敏感性将有助于实现这一目标。我们之前的研究表明，通过干扰真菌呼吸来提高念珠菌的氧化应激水平，可以提高 PDT 的效率。因此，我们试图确定临床使用的化合物，通过自身形成活性氧（ROS）来增强 PDT 引起的氧化应激。基于抗真菌咪康唑在念珠菌中诱导 ROS 的能力，我们测试了几种唑类抗真菌药在体外增强 PDT 的能力。尽管咪康唑和酮康唑都能刺激白色念珠菌产生 ROS，但只有咪康唑能增强白色念珠菌的杀伤作用，并在使用卟啉 TMP-1363 和吩噻嗪亚甲蓝作为光敏剂的 PDT 后，诱导存活的生物体产生长期的抑菌作用。数据表明，咪康唑可用于提高 PDT 对白色念珠菌的疗效，其作用机制可能是多因素的。
