Trichophyton rubrum is inhibited by free and nanoparticle encapsulated curcumin by induction of nitrosative stress after photodynamic activation

Ludmila Matos Baltazar; Aimee E Krausz; Ana Camila Oliveira Souza; Brandon L Adler; Angelo Landriscina; Tagai Musaev; Joshua D Nosanchuk; Adam J Friedman

doi:10.1371/journal.pone.0120179

Trichophyton rubrum is inhibited by free and nanoparticle encapsulated curcumin by induction of nitrosative stress after photodynamic activation

PLoS One. 2015 Mar 24;10(3):e0120179. doi: 10.1371/journal.pone.0120179. eCollection 2015.

Authors

Ludmila Matos Baltazar¹, Aimee E Krausz², Ana Camila Oliveira Souza³, Brandon L Adler², Angelo Landriscina², Tagai Musaev², Joshua D Nosanchuk¹, Adam J Friedman⁴

Affiliations

¹ 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.
² Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, United States of America.
³ Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
⁴ 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antifungal Agents / chemistry
Antifungal Agents / pharmacology
Capsules
Cell Line
Curcumin / chemistry
Curcumin / pharmacology*
Free Radical Scavengers / pharmacology
Humans
Kinetics
Light*
Microbial Sensitivity Tests
Nanoparticles / chemistry*
Phagocytosis / drug effects
Photosensitizing Agents / chemistry
Photosensitizing Agents / pharmacology
Reactive Nitrogen Species / metabolism*
Reactive Oxygen Species / metabolism
Stress, Physiological / drug effects*
Trichophyton / drug effects*
Trichophyton / growth & development
Trichophyton / metabolism
Trichophyton / radiation effects*

Substances

Antifungal Agents
Capsules
Free Radical Scavengers
Photosensitizing Agents
Reactive Nitrogen Species
Reactive Oxygen Species
Curcumin

Grants and funding

This work was funded by the Feldstein Medical Foundation. LMB and ACOS were supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.