Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Infect Dis. 2021 Sep 17;224(6):1069-1076. doi: 10.1093/infdis/jiab058.
Cutaneous mold infections commonly result from an array of traumatic injuries that involve direct inoculation of contaminated soil into wounds. Here, we explored the use of antimicrobial blue light (aBL; 405 nm wavelength) and the combination of aBL with quinine hydrochloride (aBL + Q-HCL) for the treatment of cutaneous mold infections.
Efficacy of aBL and aBL + Q-HCL in killing clinically important pathogenic molds (Aspergillus fumigatus, Aspergillus flavus, and Fusarium oxyprorum) was investigated. Ultraperformance liquid chromatography identified and quantified endogenous porphyrins in the mold conidia. Finally, a mouse model of dermabrasion wound infected with a bioluminescent variant of A. fumigatus was developed to investigate the efficacy of aBL in treating cutaneous mold infections.
We demonstrated that mold conidia are tolerant to aBL, but Q-HCL enhances efficacy. Transmission electron microscopy revealed intracellular damage by aBL. aBL + Q-HCL resulted in intracellular and cell wall damage. Porphyrins were observed in all mold strains, with A. fumigatus having the highest concentration. aBL and aBL + Q-HCL effectively reduced the burden of A. fumigatus within an established dermabrasion infection and limited recurrence posttreatment.
aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.
皮肤霉菌感染通常是由于一系列创伤性损伤引起的,这些损伤涉及将受污染的土壤直接接种到伤口中。在这里,我们探讨了使用抗菌蓝光(aBL;405nm 波长)和 aBL 与盐酸奎宁(aBL+Q-HCL)联合治疗皮肤霉菌感染的方法。
研究了 aBL 和 aBL+Q-HCL 对临床上重要的致病霉菌(烟曲霉、黄曲霉和尖孢镰刀菌)的杀灭效果。超高效液相色谱法鉴定和定量了霉菌孢子中的内源性卟啉。最后,建立了一种经皮划痕伤感染生物发光变异烟曲霉的小鼠模型,以研究 aBL 治疗皮肤霉菌感染的疗效。
我们证明霉菌孢子对 aBL 具有耐受性,但 Q-HCL 可提高其疗效。透射电子显微镜显示 aBL 可导致细胞内损伤。aBL+Q-HCL 可导致细胞内和细胞壁损伤。所有霉菌株中均观察到卟啉,其中烟曲霉的浓度最高。aBL 和 aBL+Q-HCL 可有效降低已建立的经皮划痕伤感染中烟曲霉的负担,并限制治疗后复发。
aBL 和 aBL+Q-HCL 可能为治疗霉菌感染提供一种新方法。