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Liposomal formulati...
Liposomal formulation of a new antifungal hybrid compound provides protection against Candida auris in the ex vivo skin colonization model.
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- Jaromin, Anna (author)
- Wrocław University of Economics
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- Zarnowski, Robert (author)
- University of Wisconsin-Madison
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- Markowski, Adam (author)
- Wrocław University of Economics
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- Zagórska, Agnieszka (author)
- Jagiellonian University
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- Johnson, Chad J (author)
- University of Wisconsin – Stout
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- Etezadi, Haniyeh (author)
- University of Copenhagen: Copenhagen School of Global Health
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- Kihara, Shinji (author)
- University of Copenhagen: Copenhagen School of Global Health
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- Mota-Santiago, Pablo (author)
- Lund University,Lunds universitet,Universitetsbiblioteket,Bibliotek,MAX IV-laboratoriet,Lund University Library,Library,MAX IV Laboratory
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- Nett, Jeniel E (author)
- University of Wisconsin – Stout
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- Boyd, Ben J (author)
- University of Copenhagen: Copenhagen School of Global Health
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- Andes, David R (author)
- University of Wisconsin-Madison
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 68:1
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http://dx.doi.org/10... (free)
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Keyword
- Humans
- Antifungal Agents/pharmacology
- Candida
- Candida auris
- Liposomes
- Microbial Sensitivity Tests
- Biofilms
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Jaromin, Anna
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Zarnowski, Rober ...
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Markowski, Adam
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Zagórska, Agnies ...
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Johnson, Chad J
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Etezadi, Haniyeh
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show more...
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Kihara, Shinji
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Mota-Santiago, P ...
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Nett, Jeniel E
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Boyd, Ben J
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Andes, David R
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
- Articles in the publication
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Antimicrobial Ag ...
- By the university
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Lund University