{"doi":"10.1128/aac.00955-23","title":"Liposomal formulation of a new antifungal hybrid compound provides protection against <i>Candida auris</i> in the <i>ex vivo</i> skin colonization model","abstract":"ABSTRACT 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.","journal":"Antimicrobial Agents and Chemotherapy","year":2023,"id":328519,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":320557,"name":"Robert Żarnowski","orcid":"0000-0001-6343-1500","position":1,"is_corresponding":false},{"id":1049962,"name":"Adam Markowski","orcid":"0000-0003-0610-1323","position":2,"is_corresponding":false},{"id":515072,"name":"Agnieszka Zagórska","orcid":"0000-0003-2510-7237","position":3,"is_corresponding":false},{"id":256609,"name":"Chad Johnson","orcid":"0000-0002-0017-4284","position":4,"is_corresponding":false},{"id":1049963,"name":"Haniyeh Etezadi","orcid":"0000-0003-0422-4813","position":5,"is_corresponding":false},{"id":1049964,"name":"Shinji Kihara","orcid":"0000-0001-9753-4217","position":6,"is_corresponding":false},{"id":1049965,"name":"Pablo Mota‐Santiago","orcid":"0000-0002-1537-4318","position":7,"is_corresponding":false},{"id":256616,"name":"Jeniel E. Nett","orcid":"0000-0001-8587-6244","position":8,"is_corresponding":false},{"id":1049966,"name":"Ben J. Boyd","orcid":"0000-0001-5434-590X","position":9,"is_corresponding":false},{"id":251454,"name":"David R. Andes","orcid":"0000-0002-7927-9950","position":10,"is_corresponding":false},{"id":515071,"name":"Anna Jaromin","orcid":"0000-0002-7921-8007","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:08:52.196069Z","pmid":"38092678","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}