Antibacterial activity of light triggered antibiotics against uropathogenic bacteria

在医疗实践中，广泛报道了医院感染中微生物多药耐药性的指数增长，目前已成为对公共卫生的严重威胁。尿路感染之所以重要，不仅因为其发病率高，而且因为它是开抗生素的最常见原因，这有助于耐药性的发展。抗菌素光动力疗法是一种非常有前途的替代治疗方法，可以对抗抗生素耐药菌引起的局部微生物感染。它采用一种称为光敏剂（PS）的无毒染料和低强度可见光，在分子氧的存在下能够产生细胞毒性物质。然而，为了将这种有前景的诊断和治疗方法转化为常规的临床实践，需要更多精心设计的研究，包括开发靶向光敏剂。本文提出了一种有前途的通用方法，使PS与脂多糖的选择性和特异性结合成为开发新型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了极大的兴趣。本项目的最终目的是研究定制的酞菁偶联物的结构特征、光物理特性及其在浮游和生物膜培养中对尿路致病性大肠杆菌菌株（包括多重耐药菌株）的杀伤效率之间的相互作用。PS对细菌细胞的亲和力增强，将使PS能够选择性地递送到感染部位，从而在最小的非特异性药物积累的情况下失活。

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.