Department of Microbiology and Immunology, University at Buffalo, Buffalo, New York, USA.
Photodynamic Therapy Center, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
mSphere. 2020 Jul 15;5(4):e00492-20. doi: 10.1128/mSphere.00492-20.
, , and nontypeable (NTHi) are ubiquitous upper respiratory opportunistic pathogens. Together, these three microbes are the most common causative bacterial agents of pediatric otitis media (OM) and have therefore been characterized as the primary human otopathogens. OM is the most prevalent bacterial infection in children and the primary reason for antibiotic administration in this population. Moreover, biofilm formation has been confirmed as a primary mechanism of chronic and recurrent OM disease. As bacterial biofilms are inherently metabolically recalcitrant to most antibiotics and these complex structures also present a significant challenge to the immune system, there is a clear need to identify novel antimicrobial approaches to treat OM infections. In this study, we evaluated the potential efficacy of antibacterial photodynamic therapy (aPDT) with the photosensitizer chlorin e6 (Ce6) against planktonic as well as biofilm-associated , , and NTHi. Our data indicate aPDT with Ce6 elicits significant bactericidal activity against both planktonic cultures and established biofilms formed by the three major otopathogens (with an efficacy of ≥99.9% loss of viability). Notably, the implementation of a novel, dual-treatment aPDT protocol resulted in this disinfectant effect on biofilm-associated bacteria and, importantly, inhibited bacterial regrowth 24 h posttreatment. Taken together, these data suggest this novel Ce6-aPDT treatment may be a powerful and innovative therapeutic strategy to effectively treat and eradicate bacterial OM infections and, significantly, prevent the development of recurrent disease. Otitis media (OM), or middle ear disease, is the most prevalent bacterial infection in children and the primary reason for antibiotic use and surgical intervention in the pediatric population. Biofilm formation by the major bacterial otopathogens, , , and nontypeable , has been shown to occur within the middle ears of OM patients and is a key factor in the development of recurrent disease, which may result in hearing impairment and developmental delays. Bacterial biofilms are inherently impervious to most antibiotics and present a significant challenge to the immune system. In this study, we demonstrate that antimicrobial photodynamic therapy (aPDT) using the photosensitizer chlorin e6 elicits significant bactericidal activity versus planktonic and biofilm-associated otopathogens and supports further analyses of this novel, efficacious, and promising technology as an adjunctive treatment for acute and recurrent OM.
流感嗜血杆菌、肺炎链球菌和卡他莫拉菌（NTHi）是普遍存在的上呼吸道机会性病原体。这三种微生物共同构成了小儿中耳炎（OM）最常见的细菌性致病因子，因此被认为是主要的人类耳病原体。OM 是儿童中最常见的细菌感染，也是该人群中使用抗生素的主要原因。此外，生物膜的形成已被确认为慢性和复发性 OM 疾病的主要机制。由于细菌生物膜对大多数抗生素具有内在的代谢抗性，并且这些复杂结构也对免疫系统构成重大挑战，因此显然需要确定治疗 OM 感染的新型抗菌方法。在这项研究中，我们评估了使用光敏剂氯己定（Ce6）的抗菌光动力疗法（aPDT）对浮游生物以及生物膜相关的流感嗜血杆菌、肺炎链球菌和卡他莫拉菌的潜在疗效。我们的数据表明，Ce6 的 aPDT 对三种主要耳病原体的浮游培养物和已建立的生物膜都具有显著的杀菌活性（杀菌率≥99.9%）。值得注意的是，实施一种新的双治疗 aPDT 方案可对生物膜相关细菌产生这种消毒作用，并且重要的是，可在治疗后 24 小时抑制细菌再生长。总的来说，这些数据表明，这种新型 Ce6-aPDT 治疗可能是一种强大而创新的治疗策略，可以有效治疗和根除细菌性 OM 感染，并显著预防疾病的复发。中耳炎（OM），或中耳疾病，是儿童中最常见的细菌感染，也是儿科人群中使用抗生素和手术干预的主要原因。主要细菌耳病原体流感嗜血杆菌、肺炎链球菌、卡他莫拉菌和非典型性流感嗜血杆菌在 OM 患者的中耳中形成生物膜，这是导致疾病复发的关键因素，可能导致听力障碍和发育迟缓。细菌生物膜对大多数抗生素具有固有抗性，并对免疫系统构成重大挑战。在这项研究中，我们证明使用光敏剂氯己定的抗菌光动力疗法（aPDT）对浮游生物和生物膜相关的耳病原体具有显著的杀菌活性，并支持进一步分析这种新型有效且有前途的技术作为急性和复发性 OM 的辅助治疗。
