Effect of virulence factors on the photodynamic inactivation of Cryptococcus neoformans.
Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance.
Center for Lasers and Applications, Nuclear and Energy Research Institute, São Paulo, SP, Brazil.
Renato A
RA
Prates
Beth Burgwyn
BB
Fuchs
Kazue
K
Mizuno
Qurat
Q
Naqvi
Ilka T
IT
Kato
Martha S
MS
Ribeiro
Eleftherios
E
Mylonakis
George P
GP
Tegos
Michael R
MR
Hamblin
D000935:Antifungal Agents / Q000008:administration & dosage; D002473:Cell Wall / Q000187:drug effects / Q000528:radiation effects; D060085:Coinfection / Q000382:microbiology* / Q000503:physiopathology / Q000821:virology; D003453:Cryptococcosis / Q000235:genetics / Q000382:microbiology* / Q000503:physiopathology; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000528:radiation effects; D006678:HIV / Q000472:pathogenicity; D015658:HIV Infections / Q000150:complications / Q000382:microbiology / Q000821:virology; D006801:Humans; D016867:Immunocompromised Host / Q000187:drug effects / Q000528:radiation effects; D008027:Light; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000935:Antifungal Agents; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species