Nakonieczna Joanna, Wolnikowska Katarzyna, Ogonowska Patrycja, Neubauer Damian, Bernat Agnieszka, Kamysz Wojciech
Laboratory of Molecular Diagnostics, Department of Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland.
Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, Gdańsk, Poland.
Front Microbiol. 2018 Aug 20;9:1949. doi: 10.3389/fmicb.2018.01949. eCollection 2018.
Due to the overuse of antibiotics in medicine and food production, and their targeted mechanism of action, an increasing rate in spreading of antibiotic resistance genes has been noticed. This results in inefficient therapy outcomes and higher mortality all over the world. (carbapenem-resistant) is considered one of the top three critical species according to the World Health Organization's priority pathogens list. This means that new drugs and/or treatments are needed to tackle infections caused by this bacterium. In this context search for new/alternative approaches that would overcome resistance to classical antimicrobials is of prime importance. The use of antimicrobial photodynamic inactivation (aPDI) and antimicrobial peptides (AMPs) is an efficient strategy to treat localized infections caused by multidrug-resistant . In this study, we have treated cells photodynamically in the presence and in the absence of AMP (CAMEL or pexiganan). The conditions for aPDI were as follows: rose bengal (RB) as a photosensitizing agent at 1-10 μM concentration, and subsequent irradiation with 514 nm-LED at 23 mW/cm irradiance. The analysis of cell number after the treatment has shown that the combined action of RB-mediated aPDI and cationic AMPs reduced the number of viable cells below the limit of detection (<1log CFU/ml). This was in contrast to no reduction or partial reduction after aPDI or AMP applied separately. Students -test was applied to test the statistical significance of the results. Noteworthy, our treatment proved to be effective against all 35 clinical isolates of tested within this study, including those characterized as multiresistant. Moreover, we demonstrated that such treatment is safe and does not violate the growth dynamics of human keratinocytes (77.3-97.64% survival depending on the concentration of the studied compounds or their mixtures).
由于抗生素在医学和食品生产中的过度使用及其靶向作用机制，人们注意到抗生素耐药基因的传播速率不断上升。这导致全球治疗效果不佳和死亡率升高。根据世界卫生组织的优先病原体清单，（耐碳青霉烯类）被认为是三大关键菌种之一。这意味着需要新的药物和/或治疗方法来应对由这种细菌引起的感染。在这种情况下，寻找能够克服对传统抗菌药物耐药性的新方法或替代方法至关重要。使用抗菌光动力灭活（aPDI）和抗菌肽（AMPs）是治疗由多重耐药菌引起的局部感染的有效策略。在本研究中，我们在有和没有AMP（骆驼抗菌肽或pexiganan）的情况下对细胞进行了光动力处理。aPDI的条件如下：以1-10μM浓度的孟加拉玫瑰红（RB）作为光敏剂，随后用514nm-LED以23mW/cm的辐照度进行照射。处理后细胞数量的分析表明，RB介导的aPDI和阳离子AMPs的联合作用使活细胞数量减少到检测限以下（<1log CFU/ml）。这与单独应用aPDI或AMP后没有减少或部分减少形成对比。应用学生t检验来检验结果的统计学显著性。值得注意的是，我们的治疗方法对本研究中测试的所有35株临床分离菌均有效，包括那些具有多重耐药特征的菌株。此外，我们证明这种治疗是安全的，并且不影响人角质形成细胞的生长动力学（根据所研究化合物或其混合物的浓度，存活率为77.3-97.64%）。
