Department of Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
BioLambda, Scientific and Commercial LTD, São Paulo, Brazil; Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Int J Antimicrob Agents. 2020 Jul;56(1):106025. doi: 10.1016/j.ijantimicag.2020.106025. Epub 2020 May 22.
Infections caused by hypervirulent and/or hypermucoviscous Klebsiella pneumoniae (K. pneumoniae) strains are frequently reported worldwide. Since convergence of hypervirulence and drug-resistance emerged as a serious clinical problem, novel therapeutic strategies are worthy of investigation. In this regard, antimicrobial photodynamic therapy and blue light have proven to be effective against a broad-spectrum of clinically relevant pathogens but have never been tested for hypervirulent/hypermucoviscous strains. Thus, this study investigated the influence of hypermucoviscosity and hypervirulence over the photoinactivation efficacy of blue light alone or antimicrobial photodynamic therapy mediated by methylene blue and red light.
Five clinical isolates of K. pneumoniae were screened for hypermucoviscosity by string test and for hypervirulence by a Galleria mellonella model of systemic infection. Strains were then challenged by both photoinactivation methods performed in vitro. All tests also included a non-hypervirulent/hypermucoviscous control strain for comparison.
All K. pneumoniae strains were effectively inactivated by both light-based antimicrobial strategies. Hypervirulent/hypermucoviscous strains exposed to photodynamic therapy presented rapid and consistent inactivation kinetics, while blue light led to slower and more variable inactivation kinetics.
Hypermucoviscosity and hypervirulence does not confer tolerance in K. pneumoniae against photoinactivation. Antimicrobial photodynamic therapy represents an interesting alternative to treat localised infections because it is a fast procedure with high effectiveness. On the other hand, antimicrobial blue light could be used to decontaminate hospital environments since no photosensitiser administration is required and harmful effects of ultraviolet light are avoided. Therefore, visible light-based strategies present great potential for the development of safe and effective antimicrobial technologies against such aggressive pathogens.
高毒力和/或高黏液型肺炎克雷伯菌(K. pneumoniae)引起的感染在全球范围内经常报道。由于毒力增强和耐药性的趋同已成为严重的临床问题,因此值得研究新的治疗策略。在这方面,抗菌光动力疗法和蓝光已被证明对广谱临床相关病原体有效,但从未针对高毒力/高黏液型菌株进行过测试。因此,本研究调查了高黏液性和高毒力对单独蓝光或亚甲蓝和红光介导的抗菌光动力疗法的光灭活效果的影响。
通过.string 试验筛选 5 株临床分离的肺炎克雷伯菌的高黏液性,并通过金蝇幼虫全身感染模型筛选高毒力。然后在体外对菌株进行两种光灭活方法的挑战。所有测试还包括一个非高毒力/高黏液性对照菌株进行比较。
所有肺炎克雷伯菌菌株均通过两种基于光的抗菌策略有效灭活。接受光动力疗法的高毒力/高黏液型菌株呈现出快速且一致的灭活动力学,而蓝光则导致较慢且更可变的灭活动力学。
高黏液性和高毒力并未赋予肺炎克雷伯菌对光灭活的耐受性。抗菌光动力疗法代表了一种治疗局部感染的有趣替代方法,因为它是一种快速、高效的程序。另一方面,抗菌蓝光可用于医院环境的消毒,因为不需要使用光敏剂,并且避免了紫外线的有害影响。因此,基于可见光的策略为开发针对此类侵袭性病原体的安全有效的抗菌技术提供了巨大潜力。