ArticleAntimicrobial agents and chemotherapy2016
Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Regulation of phosphatidylinositol-(4,5)-bisphosphate and active-Rho1p levels and distribution is crucial for correct spatio-temporal cytokinesis and echinocandin responses inAntimicrobial agents and chemotherapy · 2025Article
- Beyond division and morphogenesis: Considering the emerging roles of septins in plasma membrane homeostasis and cell wall integrity in human fungal pathogens.PLoS pathogens · 2025Article
- Role of cell membrane homeostasis in the pathogenicity of pathogenic filamentous fungi.Virulence · 2024Review
- Sur7 mediates a novel pathway for PIMolecular biology of the cell · 2024Article
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- Cyclic lipopeptides as membrane fusion inhibitors against SARS-CoV-2: New tricks for old dogs.Antiviral research · 2023Article
- AFM evaluation of a humanized recombinant antibody affectingRSC advances · 2023Article
- Caspofungin resistance in Candida albicans: genetic factors and synergistic compounds for combination therapies.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022Review
- Use of red, far-red, and near-infrared light in imaging of yeasts and filamentous fungi.Applied microbiology and biotechnology · 2022Review
- Genetic Screening ofFrontiers in microbiology · 2022Article
- Transcriptional regulation of the caspofungin-induced cell wall damage response in Candida albicans.Current genetics · 2020Review
- Effect of Nicotinamide AgainstFrontiers in microbiology · 2019Article
- Lipotoxicty in yeast: a focus on plasma membrane signalling and membrane contact sites.FEMS yeast research · 2018Review
- The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida albicans Cells.Journal of fungi (Basel, Switzerland) · 2017Review
- INPP5E regulates phosphoinositide-dependent cilia transition zone function.The Journal of cell biology · 2017Article
- A Linear 19-Mer Plant Defensin-Derived Peptide Acts Synergistically with Caspofungin againstFrontiers in microbiology · 2017Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] activates the yeast cell wall integrity pathway. Candida albicans exposure to caspofungin results in the rapid redistribution of PI(4,5)P2 and septins to plasma membrane foci and subsequent fungicidal effects. We studied C. albicans PI(4,5)P2 and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5)P2 and septins were visualized by live imaging of C. albicans cells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5)P2 was also visualized in GFP-PH domain-expressing C. albicans mkc1 mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5)P2 and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5)P2 levels increased in a dose-response manner at caspofungin concentrations of ≤4× MIC and progressively decreased at concentrations of ≥8× MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5)P2 and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4× MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5)P2 redistribution remained apparent in mkc1 mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at ≤4× and ≥8× MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H2O2 did not impact the PI(4,5)P2 or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5)P2-septin and PKC-Mkc1 responses that correlate with the extent of C. albicans killing, and the responses are not induced by other antifungal agents. PI(4,5)P2-septin regulation is crucial in early caspofungin responses and PKC-Mkc1 activation.
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