Cited by 38Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

Rapid redistribution of phosphatidylinositol-(4,5)-bisphosphate and septins during the Candida albicans response to caspofungin

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Badrane, Hassan, Nguyen, M. Hong, Blankenship, Jill R., Cheng, Shaoji, Hao, Binghua, Mitchell, Aaron P., Clancy, Cornelius J.·2012·Antimicrobial Agents and Chemotherapy

Abstract

We previously showed that phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and septin regulation play major roles in maintaining Candida albicans cell wall integrity in response to caspofungin and other stressors. Here, we establish a link between PI(4,5)P2 signaling and septin localization and demonstrate that rapid redistribution of PI(4,5)P2 and septins is part of the natural response of C. albicans to caspofungin. First, we studied caspofungin-hypersusceptible C. albicans irs4 and inp51 mutants, which have elevated PI(4,5)P2 levels due to loss of PI(4,5)P2-specific 5'-phosphatase activity. PI(4,5)P2 accumulated in discrete patches, rather than uniformly, along surfaces of mutants in yeast and filamentous morphologies, as visualized with a green fluorescent protein (GFP)-pleckstrin homology domain. The patches also contained chitin (calcofluor white staining) and cell wall protein Rbt5 (Rbt5-GFP). By transmission electron microscopy, patches corresponded to plasma membrane invaginations that incorporated cell wall material. Fluorescently tagged septins Cdc10 and Sep7 colocalized to these sites, consistent with well-described PI(4,5)P2-septin physical interactions. Based on expression patterns of cell wall damage response genes, irs4 and inp51 mutants were firmly positioned within a group of caspofungin-hypersusceptible, septin-regulatory protein kinase mutants. irs4 and inp51 were linked most closely to the gin4 mutant by expression profiling, PI(4,5)P2-septin-chitin redistribution and other phenotypes. Finally, sublethal 5-min exposure of wild-type C. albicans to caspofungin resulted in redistribution of PI(4,5)P2 and septins in a manner similar to those of irs4, inp51, and gin4 mutants. Taken together, our data suggest that the C. albicans Irs4-Inp51 5'-phosphatase complex and Gin4 function upstream of PI(4,5)P2 and septins in a pathway that helps govern responses to caspofungin.

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Crossref · 10.1128/aac.00112-12

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Authors
Badrane, H., Nguyen, M. H., Blankenship, J. R., Cheng, S., Hao, B., Mitchell, A. P., & Clancy, C. J.
Affiliations
  • University of Pittsburgh (US)
  • Carnegie Mellon University (US)
Venue
Antimicrobial Agents and Chemotherapy
Published
2012-09
Volume
56
Issue
9
Pages
4614-4624
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
OpenAlex
W2132219294
Cited by
38
References
61
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 1 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 2 · 2012: 1
FWCI
1.16
Type
journal article
Language
en
Open access
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • National Institute of Dental and Craniofacial Research (R56DE020831)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida albicans, phosphatidylinositol 4,5-bisphosphate, septins, caspofungin, antifungal susceptibility, cell wall integrity, plasma membrane invaginations, chitin, Cdc10
MeSH terms
Caspofungin, Antifungal Agents, Biological Transport, Candida albicans, Cell Wall, Chitin, Fungal Proteins, Phosphoric Monoester Hydrolases, Stress, Physiological, Signal Transduction, Gene Expression Regulation, Fungal, Genes, Reporter, Phosphatidylinositol Phosphates, Cyclin-Dependent Kinases, Green Fluorescent Proteins, Echinocandins, Insulin Receptor Substrate Proteins, Lipopeptides, Septins

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