Abstract：
Pathogens such as Staphylococcus aureus are able to survive in many types of host cells including phagocytes such as neutrophils and macrophages, thereby resulting in intracellular infections. Treatment of intracellular infections by conventional antimicrobials (e.g., antibiotics) is often ineffective due to low intracellular efficacy of the drugs. Thus, novel techniques which can enhance the activity of antimicrobials within cells are highly demanded. Our recent studies have shown that photochemical internalization (PCI) is a promising approach for improving the efficacy of antibiotics such as gentamicin against intracellular staphylococcal infection. In this chapter, we describe the protocols aiming to study the potential of PCI-antibiotic treatment for intracellular infections in vitro and in vivo using a RAW 264.7 cell infection model and a zebrafish embryo infection model. Proof of concept of this approach is demonstrated. The protocols are expected to prompt further development of PCI-antimicrobial based novel therapies for clinically challenging infectious diseases associated with intracellular survival of pathogens.
摘要：
病原体如金黄色葡萄球菌能够在许多类型的宿主细胞中存活,包括吞噬细胞如嗜中性粒细胞和巨噬细胞,从而导致细胞内感染。通过常规抗菌剂治疗细胞内感染（例如，抗生素）通常由于药物的细胞内功效低而无效。因此，非常需要能够增强细胞内抗菌剂活性的新技术。我们最近的研究表明，光化学内化（PCI）是一种有前途的方法，可以提高庆大霉素等抗生素对细胞内葡萄球菌感染的疗效。在这一章中,我们描述了旨在使用RAW264.7细胞感染模型和斑马鱼胚胎感染模型在体外和体内研究PCI-抗生素治疗对细胞内感染的潜力的方案.证明了这种方法的概念。预期该方案将促进用于与病原体的细胞内存活相关的具有临床挑战性的感染性疾病的基于PCI抗微生物的新疗法的进一步开发。
