Dos Anjos Carolina, Leanse Leon G, Liu Xiaojing, Miranda Hugo V, Anderson R Rox, Dai Tianhong
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Front Microbiol. 2022 Jul 12;13:932466. doi: 10.3389/fmicb.2022.932466. eCollection 2022.
is an invasive marine bacterium that causes a variety of serious infectious diseases. With the increasing multidrug-resistant variants, treatment of . infections is becoming more difficult. In this study, we explored antimicrobial blue light (aBL; 405 nm wavelength) for the treatment of infections. We first assessed the efficacy of aBL against five strains of . Next, we identified and quantified intracellular porphyrins in to provide mechanistic insights. Additionally, we measured intracellular reactive oxygen species (ROS) production and bacterial membrane permeabilization following aBL exposures. Lastly, we conducted a preclinical study to investigate the efficacy and safety of aBL for the prevention and treatment of burn infections caused by in mice. We found that aBL effectively killed in both planktonic and biofilm states, with up to a 5.17- and 4.57-log CFU reduction being achieved, respectively, following an aBL exposure of 216 J/cm. Protoporphyrin IX and coproporphyrins were predominant in all the strains. Additionally, intracellular ROS was significantly increased following aBL exposures ( < 0.01), and there was evidence of aBL-induced permeabilization of the bacterial membrane ( < 0.0001). In the preclinical studies, we found that female mice treated with aBL 30 min after bacterial inoculation showed a survival rate of 81% following 7 days of observation, while only 28% survival was observed in untreated female mice ( < 0.001). At 6 h post-inoculation, an 86% survival was achieved in aBL-treated female mice ( = 0.0002). For male mice, 86 and 63% survival rates were achieved when aBL treatment was given 30 min and 6 h after bacterial inoculation, respectively, compared to 32% survival in the untreated mice ( = 0.0004 and = 0.04). aBL did not reduce cellular proliferation or induce apoptosis. We found five cytokines were significantly upregulated in the males after aBL treatment, including MCSF ( < 0.001), MCP-5 ( < 0.01), TNF RII ( < 0.01), CXCL1 ( < 0.01), and TIMP-1 ( < 0.05), and one in the females (TIMP-1; < 0.05), suggesting that aBL may induce certain inflammatory processes. In conclusion, aBL may potentially be applied to prevent and treat infections.
是一种侵袭性海洋细菌，可导致多种严重的传染病。随着多重耐药变体的增加，治疗……感染变得更加困难。在本研究中，我们探索了抗菌蓝光（aBL；波长405nm）用于治疗……感染。我们首先评估了aBL对五株……菌株的疗效。接下来，我们鉴定并定量了……中的细胞内卟啉，以提供机制方面的见解。此外，我们测量了aBL照射后细胞内活性氧（ROS）的产生和细菌膜通透性。最后，我们进行了一项临床前研究，以调查aBL预防和治疗小鼠由……引起的烧伤感染的疗效和安全性。我们发现，aBL能有效杀死浮游状态和生物膜状态的……，在216J/cm的aBL照射后，分别实现了高达5.17和4.57个对数CFU的减少。原卟啉IX和粪卟啉在所有菌株中占主导地位。此外，aBL照射后细胞内ROS显著增加（P<0.01），并且有证据表明aBL诱导细菌膜通透性增加（P<0.0001）。在临床前研究中，我们发现细菌接种后30分钟用aBL治疗的雌性小鼠在观察7天后的存活率为81%，而未治疗的雌性小鼠仅观察到28%的存活率（P<0.001）。在接种后6小时，aBL治疗的雌性小鼠存活率达到86%（P = 0.0002）。对于雄性小鼠，细菌接种后30分钟和6小时给予aBL治疗时，存活率分别为86%和63%，相比之下未治疗小鼠的存活率为32%（P = 0.0004和P = 0.04）。aBL不会降低细胞增殖或诱导凋亡。我们发现aBL治疗后雄性小鼠中有五种细胞因子显著上调，包括MCSF（P<0.001）、MCP - 5（P<0.01）、TNF RII（P<0.01）、CXCL1（P<0.01）和TIMP - 1（P<0.05），雌性小鼠中有一种（TIMP - 1；P<0.05），这表明aBL可能诱导某些炎症过程。总之，aBL可能有潜力用于预防和治疗……感染。
