title: Trichophyton rubrum is inhibited by free and nanoparticle encapsulated curcumin by induction of nitrosative stress after photodynamic activation.
abstract: Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use against Trichophyton rubrum, a dermatophytic fungus with increasing incidence and resistance, has not been well characterized. Our aim was to evaluate the mechanism of action of aPI against T. rubrum using curcumin as the PS in both free and nanoparticle (curc-np) form. Nanocarriers stabilize curcumin and allow for enhanced solubility and PS delivery. Curcumin aPI, at optimal conditions of 10 μg/mL of PS with 10 J/cm² of blue light (417 ± 5 nm), completely inhibited fungal growth (p<0.0001) via induction of reactive oxygen (ROS) and nitrogen species (RNS), which was associated with fungal death by apoptosis. Interestingly, only scavengers of RNS impeded aPI efficacy, suggesting that curcumin acts potently via a nitrosative pathway. The curc-np induced greater NO˙ expression and enhanced apoptosis of fungal cells, highlighting curc-np aPI as a potential treatment for T. rubrum skin infections.
authors: Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Ludmila Matos
authors: LM
authors: Baltazar
authors: Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Aimee E
authors: AE
authors: Krausz
authors: Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Ana Camila Oliveira
authors: AC
authors: Souza
authors: Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Brandon L
authors: BL
authors: Adler
authors: Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Angelo
authors: A
authors: Landriscina
authors: Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Tagai
authors: T
authors: Musaev
authors: Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America; Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Joshua D
authors: JD
authors: Nosanchuk
authors: Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America; Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors: Adam J
authors: AJ
authors: Friedman
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D002214:Capsules; D002460:Cell Line; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008027:Light; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D010587:Phagocytosis / Q000187:drug effects; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects*; D014249:Trichophyton / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D000935:Antifungal Agents; D002214:Capsules; D016166:Free Radical Scavengers; D017319:Photosensitizing Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D003474:Curcumin