IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36 Km 601, X5804BYA Río Cuarto, Córdoba, Argentina.
Dr. Paula Verónica Cordero Gabrielli
IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Ruta Nacional 36 Km 601, X5804BYA Río Cuarto, Córdoba, Argentina.
Invasive candidiasis is an important cause of morbidity and mortality, and its occurrence is increasing due to the growing complexity of patients. In particular, Candida albicans exhibits several virulence factors that facilitate yeast colonization in humans. In this sense, the photodynamic inactivation of yeasts is a promising new alternative to eliminate fungal infections. Herein, the photodynamic activity sensitized by a free-base chlorin (TPCF16) and its complexes with Zn(II) (ZnTPCF16) and Pd(II) (PdTPCF16) was investigated in order to eliminate C. albicans under different forms of cell cultures. A decrease in cell survival of more than 5 log was found in planktonic cells incubated with 5 μM TPCF16 or ZnTPCF16 upon 15 min of white-light irradiation. The mechanism of action mainly involved a type II pathway in the inactivation of C. albicans cells. In addition, the photodynamic action induced by these chlorins was able to suppress the growth of C. albicans in a culture medium. These photosensitizers were also effective to photoinactivate C. albicans pseudohyphae suspended in PBS. Furthermore, the biofilms of C. albicans that incorporated the chlorins during the proliferation stage were completely eradicated using 5 μM TPCF16 or ZnTPCF16 after 60 min of light irradiation. The studies indicated that these chlorins are effective photosensitizing agents to eliminate C. albicans as planktonic cells, pseudohyphae, and biofilms.
Photocytotoxic activity sensitized by 5,10,15,20-tetrakis[4-(3-N,N-dimethylaminopropoxy)phenyl]chlorin (TAPC) was investigated in Candida albicans under different culture conditions. Planktonic cells incubated with 2.5 μM TAPC were eradicated after 5 min irradiation with white light. Studies in the presence of reactive oxygen species scavengers indicated the involvement of mainly a type II mechanism. Furthermore, cell growth of C. albicans was suppressed in the presence of 5 μM TAPC. A decrease in pseudohyphae survival of 5 log was found after 30 min irradiation. However, the photokilling of this virulence factor reached a 1.5 log reduction in human serum. The uptake of TAPC by pseudohyphae decreased in serum due to the interaction of TAPC with albumin. The binding constant of the TAPC-albumin complex was ~104 M−1, while the bimolecular quenching rate constant was ~1012 s−1 M−1, indicating that this process occurred through a static process. Thus, the photoinactivation of C. albicans was considerably decreased in the presence of albumin. A reduction of 2 log in cell survival was observed using 4.5% albumin and 30 min irradiation. The results allow optimizing the best conditions to inactivate C. albicans under different culture conditions.