Sulfone derivatives enter the cytoplasm of Candida albicans sessile cells
Authors:
- Monika Staniszewska,
- Anna Sobiepanek,
- Małgorzata Gizińska,
- Eduardo Peña-Cabrera,
- Ismael J. Arroyo-Córdoba,
- Michalina Kazek,
- Łukasz Kuryk,
- Magdalena Wieczorek,
- Mirosława Koronkiewicz,
- Tomasz Kobiela,
- Zbigniew Ochal
Abstract
Since our study showed that sulfone derivatives’ action mode creates a lesser risk of inducing widespread resistance among Candida spp., we continued verifying sulfones’ antifungal activity using the following newly synthesized derivatives: bromodichloromethy-4-hydrazinyl-3-nitrophenyl sulfone (S1), difluoroiodomethyl-4-hydrazinyl-3-nitrophenyl sulfone (S2), and chlorodifluoromethyl-4-hydrazinyl-3-nitrophenyl sulfone (S3). As the mechanism by which sulfones gain access to the cytoplasm has not been elucidated yet, in order to track S1-3, we coupled their hydrazine group with BODIPY (final S1-3 BODIPY-labelled were named SB1-3). This approach allowed us to follow the vital internalization and endocytic routing of SB1-3, while BODIPY interacts primarily with fungal surfaces, thus confirming that S1-3 and their counterparts SB1-2 behaved as non-typical agents by damaging the cell membrane and wall after being endocytosed (SB1-3 fluorescence visible inside the unlysed sessile cells). Thus greatly decreasing the likelihood of the appearance of strains resistance. Core sulfones S1-3 are a promising alternative not only to treat planktonic C. albicans but also biofilm-embedded cells. In the flow cytometric analysis, the planktonic cell surface was digested by S1-3, which made the externalized PS accessible to AnnexinV binding and PI input (accidental cell death ACD). The occurrence of ACD as well as apoptosis (crescent-shaped nuclei) and anoikis of sessile cells (regulated cell death by 100%-reduction in attachment to epithelium) was assessed through monitoring the AO/PI/HO342 markers. CLSM revealed the invasion of S1-3 and SB1-3 in C. albicans without inducing cell lysis. This was a novel approach in which QCM-D was used for real-time in situ detection of viscoelastic changes in the C. albicans biofilm, and its interaction with S1 as a representative of the sulfones tested. S1 (not toxic in vivo) is a potent fungicidal agent against C. albicans and could be administered to treat invasive candidiasis as a monotherapy or in combination with antifungal agents of reference to treat C. albicans infections.
- Record ID
- WUTbfdbf25554d949548b755260aa8079a4
- Author
- Journal series
- European Journal of Medicinal Chemistry, ISSN 0223-5234, e-ISSN 1768-3254
- Issue year
- 2020
- Vol
- 191
- Pages
- 1-16
- Publication size in sheets
- 0.75
- Article number
- 112139
- Keywords in English
- BODIPY-Labelled sulfones, Antifungals, Endocytosis, Regulated cell death, Biofilm viscoelastic changes
- ASJC Classification
- ; ; ;
- DOI
- DOI:10.1016/j.ejmech.2020.112139 Opening in a new tab
- URL
- https://pubmed.ncbi.nlm.nih.gov/32109777/ Opening in a new tab
- Language
- (en) English
- File
-
- File: 1
- wdpb_publikacje_pliki_plik_publikacja_3954_org.pdf
-
- Score (nominal)
- 140
- Score source
- journalList
- Score
- = 140.0, 16-05-2022, ArticleFromJournal
- Publication indicators
- = 8; = 0; : 2018 = 1.464; : 2020 (2 years) = 6.514 - 2020 (5 years) =6.099
- Uniform Resource Identifier
- https://repo.pw.edu.pl/info/article/WUTbfdbf25554d949548b755260aa8079a4/
- URN
urn:pw-repo:WUTbfdbf25554d949548b755260aa8079a4
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or PerishOpening in a new tab system.