Department of Pathology, Microbiology and Immunology, Vanderbilt Universitygrid.152326.1grid.412807.8grid.152326.1grid.412807.8 Medical Center, Nashville, Tennessee, USA.
Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt Universitygrid.152326.1grid.412807.8grid.152326.1grid.412807.8 Medical Center, Nashville, Tennessee, USA.
Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0091921. doi: 10.1128/AAC.00919-21. Epub 2021 Sep 13.
Staphylococcus aureus is a serious threat to public health due to the rise of antibiotic resistance in this organism, which can prolong or exacerbate skin and soft tissue infections (SSTIs). Methicillin-resistant S. aureus is a Gram-positive bacterium and a leading cause of SSTIs. As such, many efforts are under way to develop therapies that target essential biological processes in S. aureus. Antimicrobial photodynamic therapy is an effective alternative to antibiotics; therefore we developed an approach to simultaneously expose S. aureus to intracellular and extracellular photosensitizers. A near infrared photosensitizer was conjugated to human monoclonal antibodies (MAbs) that target the S. aureus iron-regulated surface determinant (Isd) heme acquisition proteins. In addition, the compound VU0038882 was developed to increase photoactivatable porphyrins within the cell. Combinatorial photodynamic treatment of drug-resistant S. aureus exposed to VU0038882 and conjugated anti-Isd MAbs proved to be an effective antibacterial strategy and in a murine model of SSTIs.
金黄色葡萄球菌由于该生物体对抗生素的耐药性上升，对公众健康构成了严重威胁，这可能会延长或加重皮肤和软组织感染（SSTIs）。耐甲氧西林金黄色葡萄球菌是一种革兰氏阳性菌，也是 SSTIs 的主要原因。因此，人们正在努力开发针对金黄色葡萄球菌重要生物过程的治疗方法。光动力抗菌疗法是抗生素的有效替代品；因此，我们开发了一种同时使金黄色葡萄球菌暴露于细胞内和细胞外光敏剂的方法。近红外光敏剂与针对金黄色葡萄球菌铁调节表面决定簇（Isd）血红素获取蛋白的人单克隆抗体（MAbs）结合。此外，还开发了化合物 VU0038882 以增加细胞内可光活化的卟啉。对耐多药金黄色葡萄球菌进行组合光动力治疗，使其暴露于 VU0038882 和结合的抗 Isd MAb 被证明是一种有效的抗菌策略，并且在 SSTIs 的小鼠模型中也是如此。
