Abstract
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.
Highlights
Fungi are common causative agents of diseases in both immune competent as well as immune compromised patient populations
Cryptococcosis is an infection caused by the yeast C. neoformans that is unique among pathogenic fungi because it produces a polysaccharide capsule to enclose the cell
We have previously reported that the susceptibility of C. neoformans to antimicrobial photodynamic inactivation (APDI) was associated with cell wall integrity [16]
Summary
Fungi are common causative agents of diseases in both immune competent as well as immune compromised patient populations. The incidence of invasive mycoses has increased significantly over the last three decades and represents an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. For these reasons systemic fungal infections still result in high attributable mortality [2]. C. neoformans causes an estimated 1 million cases of meningoencephalitis globally per year in patients with AIDS, leading to approximately 625,000 deaths [1] The bulk of this disease burden is in sub-Saharan Africa, where fatal cases of cryptococcosis may exceed deaths from tuberculosis in some areas [1]. Cranial nerve paresthesia may occur due to fungal invasion and cranial compression secondary to cerebral edema, and paralysis can persist as permanent sequelae of the disease and involves one or more cranial nerves [6,10,11,12,13]
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