Impact Factor

Original Research ARTICLE

Front. Microbiol., 08 June 2012 | http://dx.doi.org/10.3389/fmicb.2012.00193

Nitric oxide releasing nanoparticles for treatment of Candida albicans burn infections

Chitralekha Macherla1, David A. Sanchez2,3, Mohammed S. Ahmadi1,4, Ernestine M. Vellozzi1, Adam J. Friedman5, Joshua D. Nosanchuk2,3 and Luis R. Martinez1,2,3*
  • 1 Department of Biomedical Sciences, Long Island University, Brookville, NY, USA
  • 2 Divisions of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
  • 3 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
  • 4 Adelphi University, Garden City, NY, USA
  • 5 Divisions of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA

Candida albicans is a leading fungal cause of burn infections in hospital settings, and sepsis is one of the principle causes of death after a severe burn. The prevalence of invasive candidiasis in burn cases varies widely, but it accounts for 3–23% of severe infection with a mortality rate ranging from 14 to 70%. Therefore, it is imperative that we develop innovative therapeutics to which this fungus is unlikely to evolve resistance, thus curtailing the associated morbidity and mortality and ultimately improving our capacity to treat these infections. An inexpensive and stable nitric oxide (NO)-releasing nanoparticle (NO-np) platform has been recently developed. NO is known to have direct antifungal activity, modulate host immune responses and significantly regulate wound healing. In this study, we hypothesized that NO-np would be an effective therapy in the treatment of C. albicans burn infections. Using a murine burn model, NO-np demonstrated antifungal activity against C. albicans in vivo, most likely by arresting its growth and morphogenesis as demonstrated in vitro. NO-np demonstrated effective antimicrobial activity against yeast and filamentous forms of the fungus. Moreover, we showed that NO-np significantly accelerated the rate of wound healing in cutaneous burn infections when compared to controls. The histological evaluation of the affected tissue revealed that NO-np treatment modified leukocyte infiltration, minimized the fungal burden, and reduced collagen degradation, thus providing potential mechanisms for the therapeutics’ biological activity. Together, these data suggest that NO-np have the potential to serve as a novel topical antifungal which can be used for the treatment of cutaneous burn infections and wounds.

Keywords: nitric oxide, nanoparticles, burn healing, collagen, Candida albicans

Citation: Macherla C, Sanchez DA, Ahmadi MS, Vellozzi EM, Friedman AJ, Nosanchuk JD and Martinez LR (2012) Nitric oxide releasing nanoparticles for treatment of Candida albicans burn infections. Front. Microbio. 3:193. doi: 10.3389/fmicb.2012.00193

Received: 08 February 2012; Accepted: 11 May 2012;
Published online: 08 June 2012.

Edited by:

Helio K. Takahashi, Universidade Federal de Sao Paulo, Brazil

Reviewed by:

Jose M. Diaz-Minguez, Microbiologia y Genetica University of Salamanca CIALE, Spain
Simon Andrew Johnston, University of Birmingham, UK

Copyright: © 2012 Macherla, Sanchez, Ahmadi, Vellozzi, Friedman, Nosanchuk and Martinez. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: Luis R. Martinez, Long Island University, Post 720 Northern Boulevard, Pell Hall/Life Science Building, Room 347, Brookville, NY 11548-1300, USA. e-mail: luis.martinez-torres@liu.edu