AUTHOR=dos Anjos Carolina , Leanse Leon G. , Liu Xiaojing , Miranda Hugo V. , Anderson R. Rox , Dai Tianhong 

TITLE=Antimicrobial Blue Light for Prevention and Treatment of Highly Invasive Vibrio vulnificus Burn Infection in Mice

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.932466

DOI=10.3389/fmicb.2022.932466

ISSN=1664-302X

ABSTRACT=<p><italic>Vibrio vulnificus</italic> is an invasive marine bacterium that causes a variety of serious infectious diseases. With the increasing multidrug-resistant variants, treatment of <italic>V</italic>. <italic>vulnificus</italic> infections is becoming more difficult. In this study, we explored antimicrobial blue light (aBL; 405 nm wavelength) for the treatment of <italic>V. vulnificus</italic> infections. We first assessed the efficacy of aBL against five strains of <italic>V. vulnificus in vitro</italic>. Next, we identified and quantified intracellular porphyrins in <italic>V. vulnificus</italic> 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 <italic>V. vulnificus</italic> in mice. We found that aBL effectively killed <italic>V. vulnificus in vitro</italic> in both planktonic and biofilm states, with up to a 5.17- and 4.57-log<sub>10</sub> CFU reduction being achieved, respectively, following an aBL exposure of 216 J/cm<sup>2</sup>. Protoporphyrin IX and coproporphyrins were predominant in all the strains. Additionally, intracellular ROS was significantly increased following aBL exposures (<italic>P</italic> &lt; 0.01), and there was evidence of aBL-induced permeabilization of the bacterial membrane (<italic>P</italic> &lt; 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 (<italic>P</italic> &lt; 0.001). At 6 h post-inoculation, an 86% survival was achieved in aBL-treated female mice (<italic>P</italic> = 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 (<italic>P</italic> = 0.0004 and <italic>P</italic> = 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 (<italic>P</italic> &lt; 0.001), MCP-5 (<italic>P</italic> &lt; 0.01), TNF RII (<italic>P</italic> &lt; 0.01), CXCL1 (<italic>P</italic> &lt; 0.01), and TIMP-1 (<italic>P</italic> &lt; 0.05), and one in the females (TIMP-1; <italic>P</italic> &lt; 0.05), suggesting that aBL may induce certain inflammatory processes. In conclusion, aBL may potentially be applied to prevent and treat <italic>V. vulnificus</italic> infections.</p>