Eliminating Acne Through Photo-Inactivation Catalase

项目总结 寻常痤疮是一种影响80%年轻人的皮肤炎性疾病，经常会导致 即使经过适当的治疗，也会造成永久性毁容。痤疮是由荷尔蒙环境中的痤疮弧菌引起的 伴随青春期的变化和皮脂诱导。治疗学的支柱是根除 治疗痤疮和消炎。然而，治疗是延长的(通常持续4-8周)，并已 近年来与抗生素耐药性的出现有关。对两种一线抗生素的耐药性 克林霉素和红霉素目前的比例为30-50%。这种严峻的形势突显了尚未得到满足的 新的和更有效的治疗选择。这项第一阶段的STTR提案，通过与 George Liu实验室和Pulsethera Inc.的目标是放大这些初步发现，并设计用于治疗的原型 耐多药痤疮感染的风险。毕继新博士是生物光子学的专家。《共同的派·乔治》 刘(医学博士)是研究细菌中包括过氧化氢酶在内的生色团的先驱，也是第一个发现 金黄色葡萄球菌中葡萄黄素的抗氧化性。刘和程正在进行合作，开发 新型抗菌光疗法(科学进展，2020年，7：1903117)。最近两家公司之间的合作 加州大学圣地亚哥分校的乔治·刘实验室和波士顿大学的郑继新实验室发现，过氧化氢酶自然表达于 广谱细菌(革兰氏阴性和革兰氏阳性)和真菌种类，可被灭活 蓝光LED和更有效的脉冲蓝光(手稿在准备中)。因此，我们观察到 过氧化氢酶的光灭活有效地使包括痤疮球菌在内的病原体对非常低的浓度敏感。 过氧化氢的含量。研究小组的中心假设是，过氧化氢酶的光灭活能够使C. 痤疮病原体对产生ROS的免疫细胞和抗菌剂的作用。为了检验这一假设，我们首先 开发过氧化氢酶光灭活原型，验证其协同杀灭痤疮弧菌的效率 过氧化氢(目标1)。然后，我们将确定过氧化氢酶光灭活与 体内过氧化治疗痤疮的动物模型(目标2)。通过完成拟议的研究，它 我们的期望是加速消除促炎性痤疮念珠菌将带来更好的结果 并消除了导致抗生素耐药性的长疗程抗生素的需要。

PROJECT SUMMARY Acne vulgaris is a skin inflammatory condition affecting 80% of young adults and can frequently induce permanent disfigurement even with appropriate treatment. Acne is caused by C. acnes in the setting of hormonal changes and sebum induction that accompany adolescence. The mainstay of therapeutics consist of eradicating C. acnes and reducing inflammation. However, treatment is prolonged (usually 4-8 weeks in duration) and has been associated in recent years with the emergence of antibiotic resistance. Resistance to two first line antibiotics clindamycin and erythromycin currently stands at 30-50%. This severe situation highlights an unmet need for novel and more effective treatment options. This phase I STTR proposal, through a partnership between the George Liu lab and Pulsethera Inc, aims to amplify these initial findings and to design a prototype for treatment of multi-drug resistant acne infections. The PI Ji-Xin Cheng (PhD) is an expert of Biophotonics. The co-PI George Liu (MD PhD) is a pioneer in the study of chromophores including catalase in bacteria and was the first to uncover staphyloxanthin’s anti-oxidant property in S. aureus. Liu and Cheng have an ongoing collaboration in developing novel antimicrobial phototherapies (Science Advances, 2020, 7:1903117). A recent collaboration between George Liu lab at UCSD and Ji-Xin Cheng lab at Boston University found that catalase, naturally expressed in a broad spectrum of bacterial (both gram-negative and gram-positive) and fungal species, can be inactivated by a blue light LED and more effectively by pulsed blue light (manuscript in prep). Consequently, we have observed that photo-inactivation of catalase effectively sensitizes pathogens including C. acne to very low concentration of hydrogen peroxide. The team’s central hypothesis is that photo-inactivation of catalase is able to sensitize C. acne pathogens to ROS-producing immune cells and antimicrobial agents. To test this hypothesis, we will first develop a catalase photo-inactivation prototype and validate its efficiency in killing C. acne in synergy with hydrogen peroxide (aim 1). We will then determine the efficacy of catalase photo-inactivation coupled with peroxide in the treatment of acne in vivo in an animal model (aim 2). By accomplishing the proposed studies, it is our expectation that accelerated elimination of the pro-inflammatory C. acnes will lead to improved outcome and obviate the need for long courses of antibiotics that are the cause of antibiotic resistance.