Chemical features of the photosensitizers new methylene blue N and S137 influence their subcellular localization and photoinactivation efficiency in Candida albicans

Author(s)

Rodrigues, Gabriela Braga ^[1] ; Pereira Brancini, Guilherme Thomaz ^[1] ; Uyemura, Sergio Akira ^[1] ; Bachmann, Luciano ^[2] ; Wainwright, Mark ^[3] ; Leite Braga, Gilberto Ubida ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Liverpool John Moores Univ, Sch Pharm & Biomol Sci, Liverpool L3 3AF, Merseyside - England

• Document type: Journal article
• Source: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY; v. 209, AUG 2020.
• Web of Science Citations: 1

Abstract

Antimicrobial photodynamic treatment (APDT) has emerged as an effective therapy against pathogenic fungi with both acquired and intrinsic resistance to commonly used antifungal agents. Success of APDT depends on the availability of effective photosensitizers capable of acting on different fungal structures and species. Among the phenothiazinium dyes tested as photoantifungals, new methylene blue N (NMBN) and the novel pentacyclic compound S137 are the most efficient. In the present study we compared the effects of APDT with NMBN and S137 on the survival of Candida albicans and employed a set of fluorescent probes (propidium iodide, FUN-1, JCS, DHR-123 and DHE) together with confocal microscopy and flow cytometry to evaluate the effects of these two chemically diverse photosensitizers on cell membrane permeability, metabolism and redox status, and mitochondrial activity. Taken together, our results indicate that, due to chemical features resulting in different lipophilicity, NMBN and S137 localize to distinct subcellular structures and hence inactivate C. albicans cells via different mechanisms. S137 localizes mostly to the cell membrane and, upon light exposure, photo-oxidizes membrane lipids. NMBN readily localizes to mitochondria and exerts its photodynamic effects there, which was observed to be a less effective way to achieve cell death at lower light fluences. (AU)

• FAPESP's process: 12/15204-8 - Mechanistic study of the photodynamic inactivation of human and plant pathogenic fungi
• Grantee: Gilberto Úbida Leite Braga
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/22933-6 - Mechanistic study of the photosensitization of Candida and Trichophyton species
• Grantee: Gabriela Braga Rodrigues
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/24305-0 - Evaluating the effects of blue and red light on the stress tolerance and the proteome of the entomopathogenic fungus Metarhizium acridum
• Grantee: Guilherme Thomaz Pereira Brancini
• Support Opportunities: Scholarships in Brazil - Doctorate