ABSTRACTCandidaspecies are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments againstCandidainfections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeastSaccharomyces cerevisiae. In this study, we monitored the viability ofCandidaspecies after treatment with a cationic conjugated polymer [poly(p-phenylene ethynylene); PPE] or oligomer [“end-only” oligo(p-phenylene ethynylene); EO-OPE] by flow cytometry in order to explore the antifungal properties of these compounds. The oligomer was found to disruptCandida albicansyeast membrane integrity independent of light activation, while PPE is able to do so only in the presence of light, allowing for some control as to the manner in which cytotoxic effects are induced. The contrast in killing efficacy between the two compounds is likely related to their size difference and their intrinsic abilities to penetrate the fungal cell wall. Unlike EO-OPE-DABCO (where DABCO is quaternized diazabicyclo[2,2,2]octane), PPE-DABCO displayed a strong propensity to associate with soluble β-glucan, which is expected to inhibit its ability to access and perturb the inner cell membrane ofCandidayeast. Furthermore, treatment with PPE-DABCO unmaskedCandida albicansβ-glucan and increased phagocytosis by Dectin-1-expressing HEK-293 cells. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenicCandidayeast cells while also exhibiting immunostimulatory effects.
Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure
