Exploring the efficacy of novel photobactericidals against planktonic and biofilm growing uropathogenic bacteria

在世界范围内，成千上万的患者患有尿路感染(UTI)。目前对尿路感染的治疗通常是基于高浓度的全身应用抗生素。这种治疗的一个缺点是促进了(多)耐药性的发展。抗菌光动力疗法是一种替代的、基于非抗生素的治疗方法，它使我们能够以非常有效的方式应对当前的挑战；它不会导致耐药突变的选择，并且可以通过光敏剂和近红外光的联合作用在短时间内消灭病原体。光敏剂与脂多糖的选择性和特异性结合被认为是特别有吸引力的靶点，这是对我们之前寻找PSS的补充，PSS可能被认为是光灭活革兰氏阴性细菌的良好候选者。我们的目标是调整光敏剂的化学结构，使其能够在低浓度下被革兰氏阴性菌迅速吸收，并在不损害宿主组织的情况下杀死微生物。蛋白质组学分析将被用来增加我们对微生物被光灭活的顺序步骤的洞察。细菌生物膜对抗生素治疗的耐药性是那些感染UTI的人未来极易感染的主要原因之一。在这个项目中，我们的目标是在光动力作用下分散形成的生物膜。此外，我们将使用光敏剂开发创新的自我调节涂层，以预防和治疗导管相关的尿路感染。将确定光敏剂和模型表面对一系列临床上重要的革兰氏阴性菌的光细胞毒性特性。

Worldwide thousands of patients suffer from urinary tract infection (UTI). Current treatments of UTI are commonly based on high concentration of systemically applied antibiotics. A disadvantage in this treatment lies in the promoted development of (multi)resistances. Antimicrobial photodynamic therapy is alternative, non-antibiotic based treatment method that allows us to meet current challenges in a very effective way; it does not lead to the selection of resistant mutants and can destroy pathogens in a short time frame by the combined action of a photosensitizer and near infrared light. The selective and specific binding of photosensitizer to lipopolysaccharides as particularly attractive targets is envisaged, complementing our previous work on the search for PSs that might be considered good candidates for the photoinactivation of Gram-negative bacteria. We aim to modulate the chemical structure of photosensitizers so that they can be rapidly taken up by Gram-negative bacteria at low concentrations and kill microorganisms but not damage the host tissue. The proteomic analysis will be used to increase our insight into the sequential steps by which microorganisms are photoinactivated. The resistance of bacterial biofilms against antibiotic treatment is one of the major reasons why those who get UTI are highly susceptible to getting more in the future. In this project, we aim to disperse formed biofilms upon photodynamic action. In addition, we will use the photosensitizers for the development of innovative, self-regulated coatings to prevent and treat catheter-associated urinary tract infections. Photocytotoxic characteristics of photosensitizers and model surfaces against a range of clinically important Gram-negative bacteria will be determined.