Nitric Oxide-Releasing Nanoparticles Are Similar to Efinaconazole in Their Capacity to Eradicate Trichophyton rubrum Biofilms

Author(s)

Costa-Orlandi, Caroline Barcelos ^{[1, 2]} ; Martinez, Luis R. ^[3] ; Bila, Niura Madalena ^{[2, 4]} ; Friedman, Joel M. ^[5] ; Friedman, Adam J. ^{[5, 6, 7]} ; Mendes-Giannini, Maria Jose S. ^[2] ; Nosanchuk, Joshua D. ^{[8, 1]}

Affiliation

^[1] Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10461 - USA

^[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Clin Anal, Araraquara, SP - Brazil

^[3] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 - USA

^[4] Univ Eduardo Mondlane UEM, Sch Vet, Dept Paraclin, Maputo - Mozambique

^[5] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY - USA

^[6] George Washington Sch Med & Hlth Sci, Dept Dermatol, Washington, DC - USA

^[7] Albert Einstein Coll Med, Dept Med, Div Dermatol, Bronx, NY - USA

^[8] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 - USA

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY; v. 11, JUL 15 2021.
• Web of Science Citations: 0

Abstract

Filamentous fungi such as Trichophyton rubrum and T. mentagrophytes, the main causative agents of onychomycosis, have been recognized as biofilm- forming microorganisms. Nitric oxide-releasing nanoparticles (NO-np) are currently in development for the management of superficial and deep bacterial and fungal infections, with documented activity against biofilms. In this context, this work aimed to evaluate, for the first time, the in vitro anti-T. rubrum biofilm potential of NO-np using standard ATCC MYA-4438 and clinical BR1A strains and compare it to commonly used antifungal drugs including fluconazole, terbinafine and efinaconazole. The biofilms formed by the standard strain produced more biomass than those from the clinical strain. NO-np, fluconazole, terbinafine, and efinaconazole inhibited the in vitro growth of planktonic T. rubrum cells. Similarly, NO-np reduced the metabolic activities of clinical strain BR1A preformed biofilms at the highest concentration tested (SMIC50 = 40 mg/mL). Scanning electron and confocal microscopy revealed that NO-np and efinaconazole severely damaged established biofilms for both strains, resulting in collapse of hyphal cell walls and reduced the density, extracellular matrix and thickness of the biofilms. These findings suggest that biofilms should be considered when developing and testing new drugs for the treatment of dermatophytosis. Development of a biofilm phenotype by these fungi may explain the resistance of dermatophytes to some antifungals and why prolonged treatment is usually required for onychomycosis. (AU)

• FAPESP's process: 18/02785-9 - Dermatophytes and Dermatophytosis: biofilm formation and development of control strategies.
• Grantee: Maria José Soares Mendes Giannini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/18388-6 - Role of biofilm in the pathogenesis of dermatophytosis and development of combat strategies
• Grantee: Caroline Barcelos Costa Orlandi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/22188-8 - Evaluation of the interaction of biofilms mono and dual-species of Candida spp and dermatophytes photodynamic therapy combined with 2-chalcone
• Grantee: Níura Madalena Bila
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)