Antibacterial activity of light triggered antibiotics against uropathogenic bacteria

光引发抗生素对尿路致病菌的抗菌活性

• 批准号: 299246075
• 负责人: Professorin Dr. Anzhela Galstyan
• 金额: --
• 依托单位: WISNA-Juniorprofessur für Nanomaterialien in aquatischen Systemen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/299246075?language=en
• 关键词: Antibacterial; activity; light; triggered; antibiotics

The exponential growth of microbial multidrug resistance in nosocominal infections has been extensively reported in medical practice and has currently emerged as a serious threat to public health. Infections of the urinary tract are significant not only due to their high incidence, but also for being the most common reason to prescribe antibiotics, which contributes to the development of resistances. Antimicrobial photodynamic therapy represents a highly promising alternative treatment against localized microbial infections caused by antibiotic resistant bacteria. It employs a non-toxic dye termed a photosensitizer (PS) and low-intensity visible light, which in the presence of molecular oxygen is able to produce cytotoxic species. Yet, in order to transfer this promising diagnostic and therapeutic method to regular clinical practice, additional well-designed studies are needed, including the development of targeted photosensitizers. Herein, a promising general approach is proposed to enable the selective and specific binding of PS to lipopolysaccharides as particularly attractive targets for the development of new antibacterial agents. Besides providing a protective barrier, lipopolysaccharides are of great interest due to their potent inflammatory effects and their contribution to biofilm formation. The final aim of this project is to investigate the interplay between structural features of tailored phthalocyanine conjugates, their photophysical properties and their killing efficiency against uropathogenic E. coli strains including multiresistant isolates in planktonic and biofilm cultures. The enhanced affinity of the PS for bacterial cells will enable a selective delivery of PS to the infection site leading to inactivation with minimal non-specific drug accumulation.

医院感染中微生物多药耐药性的指数增长在医学实践中得到了广泛的报道，目前已成为对公众健康的严重威胁。尿路感染很重要，不仅因为其发病率高，而且还因为它是开抗生素的最常见原因，这导致了耐药性的产生。抗菌光动力疗法是治疗由抗生素耐药细菌引起的局部微生物感染的一种非常有前途的替代疗法。它使用一种被称为光敏剂(PS)的无毒染料和低强度可见光，在分子氧存在的情况下，这种可见光能够产生细胞毒性物质。然而，为了将这种有希望的诊断和治疗方法转化为常规的临床实践，还需要更多精心设计的研究，包括开发靶向光敏剂。在此，提出了一种有希望的通用方法，使PS选择性和特异性地结合到脂多糖上，作为开发新抗菌剂的特别有吸引力的靶点。除了提供保护屏障外，脂多糖由于其强大的炎症作用和对生物膜形成的贡献而引起人们的极大兴趣。本项目的最终目的是研究定制的酞菁结合物的结构特征、它们的光物理性质和它们在浮游和生物膜培养中对包括多重耐药菌株在内的致尿系大肠杆菌的杀灭效率之间的相互作用。PS对细菌细胞亲和力的增强将使PS能够选择性地输送到感染部位，从而以最小的非特异性药物积累来灭活PS。

项目成果

Conjugated phthalocyanines as light driven antibiotics

共轭酞菁作为光驱动抗生素

• DOI: 10.1016/j.pdpdt.2017.01.124
• 发表时间: 2017
• 期刊: Photodiagnosis and Photodynamic Therapy
• 影响因子: 3.3
• 作者: A. Galstyan;D. Block;S. Niemenn;K. Riehemann;C.A. Strassert;A. Faust;M. Schäfers;U. Dobrindt
• 通讯作者: U. Dobrindt

Making and Breaking Barriers to Overcome Microbial Infections

建立和打破克服微生物感染的障碍

• DOI: 10.1364/omp.2017.omw3d.4
• 发表时间: 2017
• 作者: A Galstyan;R Schiller;U Dobrindt
• 通讯作者: U Dobrindt