Leon G Leanse1,2, Carolina Dos Anjos1,2,3, Ying Wang4, Clinton K Murray5, David C Hooper6, Tianhong Dai1,2. 1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. 3. Department of Internal Medicine, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil. 4. Department of Laser Medicine, The First Medical Center, Chinese PLA General Hospital, Beijing, China. 5. 1st Area Medical Laboratory, Aberdeen Proving Ground, Aberdeen, Maryland, USA. 6. Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: aBL and aBL + Q-HCL may offer a novel approach for the treatment of mold infections.
Authors: Leon G Leanse; Pu-Ting Dong; Xueping S Goh; Min Lu; Ji-Xin Cheng; David C Hooper; Tianhong Dai Journal: J Infect Dis Date: 2020-02-03 Impact factor: 5.226
Authors: Yucheng Wang; Ying Wang; Yuguang Wang; Clinton K Murray; Michael R Hamblin; David C Hooper; Tianhong Dai Journal: Drug Resist Updat Date: 2017-10-13 Impact factor: 18.500
Authors: Seyedmojtaba Seyedmousavi; Roger J M Brüggemann; Willem J G Melchers; Antonius J M M Rijs; Paul E Verweij; Johan W Mouton Journal: J Antimicrob Chemother Date: 2012-11-05 Impact factor: 5.790
Authors: Tianhong Dai; Asheesh Gupta; Ying-Ying Huang; Rui Yin; Clinton K Murray; Mark S Vrahas; Margaret E Sherwood; George P Tegos; Michael R Hamblin Journal: Antimicrob Agents Chemother Date: 2012-12-21 Impact factor: 5.191
Authors: Michaela Novodvorska; Malcolm Stratford; Martin J Blythe; Raymond Wilson; Richard G Beniston; David B Archer Journal: Fungal Genet Biol Date: 2016-07-01 Impact factor: 3.495
Authors: Carolina Dos Anjos; Leon G Leanse; Xiaojing Liu; Hugo V Miranda; R Rox Anderson; Tianhong Dai Journal: Front Microbiol Date: 2022-07-12 Impact factor: 6.064