ArticlePLoS pathogens2012
Candida albicans scavenges host zinc via Pra1 during endothelial invasion.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 2 of them syntheses that pooled it.
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Who cites it
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 240 citations in OpenAlex.
- Transcriptomic meta-analysis to identify potential antifungal targets in Candida albicans.BMC microbiology · 2024Pooled it
- Epidemiology and Pathophysiology of COVID-19-Associated Mucormycosis: India Versus the Rest of the World.Mycopathologia · 2021Pooled it
- Miltefosine regulates gene expression related to morphogenesis and zinc metabolism inMicrobiology spectrum · 2026Article
- Epidemiology, Diagnostics and Therapy of Vulvovaginal Fungal Infections.Pathogens (Basel, Switzerland) · 2026Review
- Formation of the intradimer disulfide bond in human calprotectin maintains metal-withholding function and tunes proteolytic susceptibility.Chemical science · 2026Article
- Vaginal PRA1 identifies clinically relevant Candida albicans vaginitis and excludes asymptomatic colonization: an exploratory study.BMC microbiology · 2026Observational
- State-of-the-Art Review: Managing Vulvovaginal Candidiasis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Review
- Genomic Analysis Reveals Diversified and Stress-Responsive Transport Repertoire inJournal of fungi (Basel, Switzerland) · 2026Article
- Cadmium is a stowaway on the zinc transporter AcZIP1 from Agaricus crocodilinus.Archives of microbiology · 2026Article
- IL-17-mediated antifungal immunity restricts Candida albicans pathogenicity in the oral cavity.Nature microbiology · 2026Article
- Structural insights into mechanisms of zinc scavenging by the Candida albicans zincophore Pra1.Nature communications · 2025Article
- A zinc-chelating cyclic alkyl polyamine compound is efficient and safe in a murine model of multidrug-resistantAntimicrobial agents and chemotherapy · 2025Article
- Characterization of Metabolomic Response ofMicroorganisms · 2025Article
- Commensalism and pathogenesis of Candida albicans at the mucosal interface.Nature reviews. Microbiology · 2025Review
- Review
- Article
- An Introduction to the Influence of Nutritional Factors on the Pathogenesis of Opportunist Fungal Pathogens in Humans.Pathogens (Basel, Switzerland) · 2025Review
- Composition, Influencing Factors, and Effects on Host Nutrient Metabolism of Fungi in Gastrointestinal Tract of Monogastric Animals.Animals : an open access journal from MDPI · 2025Review
- Comparative functional analysis of a new CDR1-like ABC transporter gene in multidrug resistance and virulence between Magnaporthe oryzae and Trichophyton mentagrophytes.Cell communication and signaling : CCS · 2025Article
- Microbial adaptive pathogenicity strategies to the host inflammatory environment.FEMS microbiology reviews · 2025Review
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ability of pathogenic microorganisms to assimilate essential nutrients from their hosts is critical for pathogenesis. Here we report endothelial zinc sequestration by the major human fungal pathogen, Candida albicans. We hypothesised that, analogous to siderophore-mediated iron acquisition, C. albicans utilises an extracellular zinc scavenger for acquiring this essential metal. We postulated that such a "zincophore" system would consist of a secreted factor with zinc-binding properties, which can specifically reassociate with the fungal cell surface. In silico analysis of the C. albicans secretome for proteins with zinc binding motifs identified the pH-regulated antigen 1 (Pra1). Three-dimensional modelling of Pra1 indicated the presence of at least two zinc coordination sites. Indeed, recombinantly expressed Pra1 exhibited zinc binding properties in vitro. Deletion of PRA1 in C. albicans prevented fungal sequestration and utilisation of host zinc, and specifically blocked host cell damage in the absence of exogenous zinc. Phylogenetic analysis revealed that PRA1 arose in an ancient fungal lineage and developed synteny with ZRT1 (encoding a zinc transporter) before divergence of the Ascomycota and Basidiomycota. Structural modelling indicated physical interaction between Pra1 and Zrt1 and we confirmed this experimentally by demonstrating that Zrt1 was essential for binding of soluble Pra1 to the cell surface of C. albicans. Therefore, we have identified a novel metal acquisition system consisting of a secreted zinc scavenger ("zincophore"), which reassociates with the fungal cell. Furthermore, functional similarities with phylogenetically unrelated prokaryotic systems indicate that syntenic zinc acquisition loci have been independently selected during evolution.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.