The Repurposing of the Antimalaria Drug, Primaquine, as a Photosensitizer to Inactivate Cryptococcal Cells

Abstract

Cryptococcal cells can manifest skin infections in immunocompromised persons. While it may be easy to diagnose cryptococcal infection, treatment often fails due to the ineffectiveness of current antifungal agents. To this end, the present study explored the repurposing of primaquine (PQ), as a photosensitizer. PDT was carried out using a germicidal ultraviolet (UV) lamp, which has a radiation output of approximately 625 µW/cm2 at a distance of 20 cm. When compared to the non-treated cells, the metabolic activity of cryptococcal cells was significantly (p < 0.05) limited. The photolytic products of PQ were observed to alter the ultrastructure of treated cells. The latter was not incidental, as the same cells were also documented to lose their selective permeability. Importantly, PDT also improved the efficiency of macrophages to kill internalized cryptococcal cells (p ≤ 0.05) when compared to non-treated macrophages. Equally importantly, PDT was not detrimental to macrophages, as their metabolic activity was not significantly (p > 0.05) limited, even when exposed to 20× the MIC (determined for cryptococcal cells) and an exposure time that was 4× longer. Taken together, the results suggest PQ has the potential to control the growth of cryptococcal cells and limit their survival inside the macrophage.