ArticleThe Journal of antimicrobial chemotherapy2022
Genotypic, proteomic, and phenotypic approaches to decipher the response to caspofungin and calcineurin inhibitors in clinical isolates of echinocandin-resistant Candida glabrata.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Whole genome sequencing analysis of Candida glabrata isolates collected from patients with selected drug-resistant candidiasis hospitalized in Eastern Poland.Folia microbiologica · 2026Article
- A Calcineurin Inhibitor as an Enhancer ofACS omega · 2026Article
- Antibiofilm activity of manogepix, ibrexafungerp, amphotericin B, rezafungin, and caspofungin againstAntimicrobial agents and chemotherapy · 2025Article
- Resilience in Resistance: The Role of Cell Wall Integrity in Multidrug-Resistant Candida.Journal of fungi (Basel, Switzerland) · 2025Review
- Antifungal Synergy: Mechanistic Insights into the R-1-R Peptide andInternational journal of molecular sciences · 2024Article
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- Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections.Pharmaceutics · 2023Review
- Glyphosate and glyphosate-based herbicides (GBHs) induce phenotypic imipenem resistance in Pseudomonas aeruginosa.Scientific reports · 2022Article
- Evaluation of Anti-Journal of fungi (Basel, Switzerland) · 2022Article
- Molecular investigations onRSC advances · 2022Article
- The Combination of Iron and Copper Increases Pathogenicity and Induces Proteins Related to the Main Virulence Factors in Clinical Isolates ofJournal of fungi (Basel, Switzerland) · 2022Article
- Article
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEchinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological processes and proteins involved in the response to caspofungin may provide clues indicating new therapeutic targets.
objectivesWe determined the resistance mechanism and assessed the proteome response to caspofungin exposure. We then evaluated the phenotypic impact of calcineurin inhibition by FK506 and cephalosporine A (CsA) on caspofungin-resistant Candida glabrata isolates.
methodsTwenty-five genes associated with caspofungin resistance were analysed by NGS, followed by studies of the quantitative proteomic response to caspofungin exposure. Then, susceptibility testing of caspofungin in presence of FK506 and CsA was performed. The effects of calcineurin inhibitor/caspofungin combinations on heat stress (40°C), oxidative stress (0.2 and 0.4 mM menadione) and on biofilm formation (polyurethane catheter) were analysed. Finally, a Galleria mellonella model using blastospores (1 × 109 cfu/mL) was developed to evaluate the impact of the combinations on larval survival.
resultsF659-del was found in the FKS2 gene of resistant strains. Proteomics data showed some up-regulated proteins are involved in cell-wall biosynthesis, response to stress and pathogenesis, some of them being members of calmodulin-calcineurin pathway. Therefore, the impact of calmodulin inhibition was explored. Calmodulin inhibition restored caspofungin susceptibility, decreased capacity to respond to stress conditions, and reduced biofilm formation and in vivo pathogenicity.
conclusionsOur findings confirm that calmodulin-calcineurin-Crz1 could provide a relevant target in life-threatening invasive candidiasis.
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