Simple view
Full metadata view
Authors
Statistics
Liposomal formulation of a new antifungal hybrid compound provides protection against Candida auris in the ex vivo skin colonization model
candida auris
biofilm
antifungal
proteomics
liposomes
fungal skin infection
The newly emerged pathogen, Candida auris, presents a serious threat to public health worldwide. This multidrug-resistant yeast often colonizes and persists on the skin of patients, can easily spread from person to person, and can cause life-threatening systemic infections. New antifungal therapies are therefore urgently needed to limit and control both superficial and systemic C. auris infections. In this study, we designed a novel antifungal agent, PQA-Az-13, that contains a combination of indazole, pyrrolidine, and arylpiperazine scaffolds substituted with a trifluoromethyl moiety. PQA-Az-13 demonstrated antifungal activity against biofilms of a set of 10 different C. auris clinical isolates, representing all four geographical clades distinguished within this species. This compound showed strong activity, with MIC values between 0.67 and 1.25 µg/mL. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes composed of soybean phosphatidylcholine (SPC), 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP), and N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt (DSPE-PEG 2000), and characterized by biophysical and spectral techniques. These PQA-Az-13-loaded liposomes displayed a mean size of 76.4 nm, a positive charge of +45.0 mV, a high encapsulation efficiency of 97.2%, excellent stability, and no toxicity to normal human dermal fibroblasts. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models. These initial results suggest that molecules like PQA-Az-13 warrant further study and development.
| dc.abstract.en | The newly emerged pathogen, Candida auris, presents a serious threat to public health worldwide. This multidrug-resistant yeast often colonizes and persists on the skin of patients, can easily spread from person to person, and can cause life-threatening systemic infections. New antifungal therapies are therefore urgently needed to limit and control both superficial and systemic C. auris infections. In this study, we designed a novel antifungal agent, PQA-Az-13, that contains a combination of indazole, pyrrolidine, and arylpiperazine scaffolds substituted with a trifluoromethyl moiety. PQA-Az-13 demonstrated antifungal activity against biofilms of a set of 10 different C. auris clinical isolates, representing all four geographical clades distinguished within this species. This compound showed strong activity, with MIC values between 0.67 and 1.25 µg/mL. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes composed of soybean phosphatidylcholine (SPC), 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP), and N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, sodium salt (DSPE-PEG 2000), and characterized by biophysical and spectral techniques. These PQA-Az-13-loaded liposomes displayed a mean size of 76.4 nm, a positive charge of +45.0 mV, a high encapsulation efficiency of 97.2%, excellent stability, and no toxicity to normal human dermal fibroblasts. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models. These initial results suggest that molecules like PQA-Az-13 warrant further study and development. | |
| dc.affiliation | Wydział Farmaceutyczny : Zakład Chemii Leków | pl |
| dc.cm.date | 2024-01-10T23:16:36Z | |
| dc.cm.id | 114146 | pl |
| dc.cm.idOmega | UJCMc7c7d45f4c61430bb42e8a99d7b01d45 | pl |
| dc.contributor.author | Jaromin, Anna | pl |
| dc.contributor.author | Robert, Zarnowski | pl |
| dc.contributor.author | Adam, Markowski | pl |
| dc.contributor.author | Zagórska, Agnieszka - 133872 | pl |
| dc.contributor.author | J., Johnson Chad | pl |
| dc.contributor.author | Haniyeh, Etezadi | pl |
| dc.contributor.author | Shinji, Kihara | pl |
| dc.contributor.author | Pablo, Mota-Santiago | pl |
| dc.contributor.author | E., Nett Jeniel | pl |
| dc.contributor.author | J., Boyd Ben | pl |
| dc.contributor.author | R., Andes David | pl |
| dc.date.accession | 2024-01-10 | pl |
| dc.date.accessioned | 2024-01-10T23:16:36Z | |
| dc.date.available | 2024-01-10T23:16:36Z | |
| dc.date.issued | 2024 | pl |
| dc.date.openaccess | 0 | |
| dc.description.accesstime | w momencie opublikowania | |
| dc.description.number | 1 | pl |
| dc.description.version | ostateczna wersja wydawcy | |
| dc.description.volume | 68 | pl |
| dc.identifier.articleid | e00955-23 | pl |
| dc.identifier.doi | 10.1128/aac.00955-23 | pl |
| dc.identifier.eissn | 1098-6596 | pl |
| dc.identifier.issn | 0066-4804 | pl |
| dc.identifier.uri | https://ruj.uj.edu.pl/xmlui/handle/item/325301 | |
| dc.identifier.weblink | https://journals.asm.org/doi/10.1128/aac.00955-23 | pl |
| dc.language | eng | pl |
| dc.language.container | eng | pl |
| dc.pbn.affiliation | Dziedzina nauk medycznych i nauk o zdrowiu : nauki farmaceutyczne | |
| dc.rights | Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa | |
| dc.rights.licence | CC-BY | |
| dc.rights.simpleview | Wolny dostęp | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/legalcode.pl | |
| dc.share.type | Otwarte czasopismo | |
| dc.source.integrator | false | |
| dc.subject.en | candida auris | |
| dc.subject.en | biofilm | |
| dc.subject.en | antifungal | |
| dc.subject.en | proteomics | |
| dc.subject.en | liposomes | |
| dc.subject.en | fungal skin infection | |
| dc.subtype | Article | pl |
| dc.title | Liposomal formulation of a new antifungal hybrid compound provides protection against Candida auris in the ex vivo skin colonization model | pl |
| dc.title.journal | Antimicrobial Agents and Chemotherapy | pl |
| dc.type | JournalArticle | pl |
| dspace.entity.type | Publication |
* The migration of download and view statistics prior to the date of April 8, 2024 is in progress.
Views
11
Views per month
Views per city
Downloads
Open Access