Chan Ben Chung Lap, Dharmaratne Priyanga, Wang Baiyan, Lau Kit Man, Lee Ching Ching, Cheung David Wing Shing, Chan Judy Yuet Wa, Yue Grace Gar Lee, Lau Clara Bik San, Wong Chun Kwok, Fung Kwok Pui, Ip Margaret
Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong 999077, China.
Department of Microbiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong 999077, China.
Pharmaceutics. 2021 Sep 3;13(9):1399. doi: 10.3390/pharmaceutics13091399.
High prevalence rates of methicillin-resistant (MRSA) and lack of effective antibacterial treatments urge discovery of alternative therapeutic modalities. The advent of antibacterial photodynamic therapy (aPDT) is a promising alternative, composing rapid, nonselective cell destruction without generating resistance. We used a panel of clinically relevant MRSA to evaluate hypericin (Hy) and pheophobide a (Pa)-mediated PDT with clinically approved methylene blue (MB). We translated the promising in vitro anti-MRSA activity of selected compounds to a full-thick MRSA wound infection model in mice (in vivo) and the interaction of aPDT innate immune system (cytotoxicity towards neutrophils). Hy-PDT consistently displayed lower minimum bactericidal concentration (MBC) values (0.625-10 µM) against ATCC RN4220/pUL5054 and a whole panel of community-associated (CA)-MRSA compared to Pa or MB. Interestingly, Pa-PDT and Hy-PDT topical application demonstrated encouraging in vivo anti-MRSA activity (>1 log CFU reduction). Furthermore, histological analysis showed wound healing via re-epithelization was best in the Hy-PDT group. Importantly, the dark toxicity of Hy was significantly lower ( < 0.05) on neutrophils compared to Pa or MB. Overall, Hy-mediated PDT is a promising alternative to treat MRSA wound infections, and further rigorous mechanistic studies are warranted.
耐甲氧西林金黄色葡萄球菌（MRSA）的高流行率以及缺乏有效的抗菌治疗方法促使人们去发现替代治疗方式。抗菌光动力疗法（aPDT）的出现是一种很有前景的替代方法，它能快速、非选择性地破坏细胞且不会产生耐药性。我们使用一组临床相关的MRSA菌株，以临床批准的亚甲蓝（MB）为对照，评估金丝桃素（Hy）和脱镁叶绿酸a（Pa）介导的光动力疗法。我们将所选化合物在体外有前景的抗MRSA活性转化到小鼠全层MRSA伤口感染模型（体内）中，并研究了aPDT与先天免疫系统的相互作用（对中性粒细胞的细胞毒性）。与Pa或MB相比，Hy-PDT对ATCC RN4220/pUL5054以及一组社区获得性（CA）-MRSA始终显示出更低的最低杀菌浓度（MBC）值（0.625 - 10 µM）。有趣的是，Pa-PDT和Hy-PDT局部应用在体内显示出令人鼓舞的抗MRSA活性（CFU减少>1个对数）。此外，组织学分析表明，Hy-PDT组通过重新上皮化实现伤口愈合的效果最佳。重要的是，与Pa或MB相比，Hy对中性粒细胞的暗毒性显著更低（<0.05）。总体而言，Hy介导的光动力疗法是治疗MRSA伤口感染的一种有前景的替代方法，有必要进行进一步严格的机制研究。
