Biomedical Engineering, Texas A&M University, College Station, TX 77840.
Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
Proc Natl Acad Sci U S A. 2022 Sep 6;119(36):e2208378119. doi: 10.1073/pnas.2208378119. Epub 2022 Aug 29.
The widespread use of antibiotics drives the evolution of antimicrobial-resistant bacteria (ARB), threatening patients and healthcare professionals. Therefore, the development of novel strategies to combat resistance is recognized as a global healthcare priority. The two methods to combat ARB are development of new antibiotics or reduction in existing resistances. Development of novel antibiotics is a laborious and slow-progressing task that is no longer a safe reserve against looming risks. In this research, we suggest a method for reducing resistance to extend the efficacious lifetime of current antibiotics. Antimicrobial photodynamic therapy (aPDT) is used to generate reactive oxygen species (ROS) via the photoactivation of a photosensitizer. ROS then nonspecifically damage cellular components, leading to general impairment and cell death. Here, we test the hypothesis that concurrent treatment of bacteria with antibiotics and aPDT achieves an additive effect in the elimination of ARB. Performing aPDT with the photosensitizer methylene blue in combination with antibiotics chloramphenicol and tetracycline results in significant reductions in resistance for two methicillin-resistant (MRSA) strains, USA300 and RN4220. Additional resistant strain and antibiotic combinations reveal similar results. Taken together, these results suggest that concurrent aPDT consistently decreases resistance by improving susceptibility to antibiotic treatment. In turn, this development exhibits an alternative to overcome some of the growing MRSA challenge.
抗生素的广泛使用推动了抗微生物耐药细菌（ARB）的进化，威胁着患者和医护人员的健康。因此，开发新的策略来对抗耐药性被认为是全球医疗保健的优先事项。对抗 ARB 的两种方法是开发新的抗生素或减少现有耐药性。开发新的抗生素是一项艰巨而进展缓慢的任务，它不再是应对迫在眉睫的风险的安全储备。在这项研究中，我们提出了一种减少耐药性的方法，以延长现有抗生素的有效寿命。抗菌光动力疗法（aPDT）通过光敏剂的光激活产生活性氧（ROS）。然后，ROS 非特异性地损伤细胞成分，导致普遍损伤和细胞死亡。在这里，我们测试了一个假设，即同时用抗生素和 aPDT 治疗细菌可以在消除 ARB 方面产生附加效应。用光敏剂亚甲蓝进行 aPDT 联合抗生素氯霉素和四环素治疗两种耐甲氧西林金黄色葡萄球菌（MRSA）菌株 USA300 和 RN4220，可显著降低耐药性。其他耐药菌株和抗生素组合也显示出类似的结果。总之，这些结果表明，同时进行 aPDT 通过提高对抗生素治疗的敏感性，一致降低耐药性。反过来，这种发展为克服日益严重的 MRSA 挑战提供了一种替代方案。
