title: Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure.
abstract: Candida species 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 against Candida infections 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 yeast Saccharomyces cerevisiae In this study, we monitored the viability of Candida species 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 disrupt Candida albicans yeast 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 of Candida yeast. Furthermore, treatment with PPE-DABCO unmasked Candida albicans β-glucan and increased phagocytosis by Dectin-1-expressing HEK-293 cells. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenic Candida yeast cells while also exhibiting immunostimulatory effects.
authors.affiliation: Department of Nanoscience & Microsystems Engineering, University of New Mexico, Albuquerque, New Mexico, USA Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Pappas
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA Department of Chemical & Biological Engineering, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Rina
authors.initials: R
authors.lastname: Sylejmani
authors.affiliation: Department of Nanoscience & Microsystems Engineering, University of New Mexico, Albuquerque, New Mexico, USA Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Graus
authors.affiliation: Department of Nanoscience & Microsystems Engineering, University of New Mexico, Albuquerque, New Mexico, USA Department of Chemical & Biological Engineering, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Donabedian
authors.affiliation: Department of Chemical & Biological Engineering, University of New Mexico, Albuquerque, New Mexico, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Whitten
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA akneumann@salud.unm.edu.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Neumann
mesh_terms: D000480:Alkynes / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000235:genetics; D004987:Ethers / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D047071:beta-Glucans / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D000480:Alkynes; D000935:Antifungal Agents; D004987:Ethers; D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1; C436384:phenyleneethynylene