{"doi":"10.1093/mtomcs/mfad070","title":"Histatin-5 interacts with cellular copper to promote antifungal activity against <i>Candida albicans</i>","abstract":"Histatin-5 (Hist-5) is an antimicrobial peptide found in human saliva that functions to defend the oral cavity from microbial infections, such as those caused by the fungal pathogen Candida albicans (C. albicans). Hist-5 can bind Cu in multiple oxidation states, Cu2+ and Cu+in vitro, and supplemental Cu2+ has been shown to improve the fungicidal activity of the peptide against C. albicans in culture. However, the exact role of Cu on the antifungal activity of Hist-5 and whether direct peptide-Cu interactions occur intracellularly has yet to be fully determined. Here, we used a combination of fluorescence spectroscopy and confocal microscopy experiments to show reversible Cu-dependent quenching of a fluorescent Hist-5 analogue, Hist-5*, indicating a direct interaction between Hist-5 and intracellular Cu. X-ray fluorescence microscopy images revealed peptide-induced changes to cellular Cu distribution and cell-associated Cu content. These data support a model in which Hist-5 can facilitate the hyperaccumulation of Cu in C. albicans and directly interact with Cu intracellularly to increase the fungicidal activity of Hist-5.","journal":"Metallomics","year":2023,"id":341964,"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":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":1078008,"name":"Natalie B. Schulte","orcid":"0000-0003-4274-4289","position":1,"is_corresponding":false},{"id":566132,"name":"Barry Lai","orcid":"0000-0002-6061-7155","position":2,"is_corresponding":false},{"id":1078009,"name":"Hugh H. Harris","orcid":"0000-0002-3472-8628","position":3,"is_corresponding":false},{"id":364225,"name":"Katherine J. Franz","orcid":"0000-0002-9015-0998","position":4,"is_corresponding":false},{"id":1078007,"name":"Joanna X. Campbell","orcid":"0000-0002-0533-075X","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:11:08.077724Z","pmid":"38061812","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":[]}