Related Experiment Video

Updated: Sep 25, 2025

Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
09:44

Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis

Published on: June 13, 2021

2.8K

Plasma Membrane Phosphatidylinositol 4-Phosphate Is Necessary for Virulence of Candida albicans

James B Konopka1

  • 1Department of Microbiology and Immunology, Stony Brook University, Stony Brook, New York, USA.

Mbio
|April 25, 2022
PubMed

Insights

Phosphatidylinositol 4-phosphate (PI4P) in Candida albicans regulates hyphal growth and cell wall organization. Disrupting PI4P impacts disseminated fungal infections but not oral infections, revealing site-specific virulence roles.

Area of Science:

  • Mycology
  • Cell Biology
  • Infectious Diseases

Background:

  • Phosphatidylinositol lipids, including phosphatidylinositol 4-phosphate (PI4P), are crucial regulators of fundamental cellular processes such as vesicle trafficking and cell polarity.
  • While PI4P's roles in the Golgi apparatus are well-established, its specific functions at the plasma membrane are less understood, particularly in pathogenic fungi.
  • Candida albicans, a significant human fungal pathogen, presents a unique opportunity to study plasma membrane PI4P due to the ability to selectively target its production.

Purpose of the Study:

  • To investigate the novel roles of phosphatidylinositol 4-phosphate (PI4P) in the plasma membrane of Candida albicans.
  • To determine the impact of altered PI4P levels on fungal virulence in different host environments.
  • To elucidate the mechanisms by which PI4P affects fungal cell biology and host-pathogen interactions.

Main Methods:

  • Genetic manipulation of the STT4 kinase in Candida albicans to selectively eliminate the plasma membrane pool of PI4P.
  • Phenotypic analysis of the resulting stt4Δ mutant, focusing on polarized hyphal growth and cell wall organization.
  • Assessment of fungal virulence using murine models of disseminated candidiasis and oral candidiasis.

Main Results:

  • Selective elimination of plasma membrane PI4P in C. albicans via STT4 deletion impaired polarized hyphal growth and altered cell wall organization.
  • stt4Δ mutants exhibited a significant defect in disseminated candidiasis in a murine model.
  • Conversely, stt4Δ mutants showed no defect in an oral infection model.
  • The increased susceptibility to disseminated infection was hypothesized to be due to abnormal exposure of β-glucan in the mutant cell walls, leading to enhanced innate immune cell recruitment.

Conclusions:

  • Plasma membrane PI4P plays critical roles in Candida albicans hyphal morphogenesis and cell wall integrity.
  • The virulence of C. albicans is site-specific, with plasma membrane PI4P being essential for disseminated infections but not oral infections.
  • These findings underscore the importance of evaluating fungal pathogen virulence across diverse host niches and highlight PI4P as a potential therapeutic target.
Keywords:
Candida albicansSTT4fungalhyphaephosphatidylinositolphosphatidylinositol 4-phosphate

More Related Videos

Clarifying and Imaging Candida albicans Biofilms11:09

Clarifying and Imaging Candida albicans Biofilms

Published on: March 6, 2020

11.8K
Live-cell Video Microscopy of Fungal Pathogen Phagocytosis08:52

Live-cell Video Microscopy of Fungal Pathogen Phagocytosis

Published on: January 9, 2013

39.5K

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.8K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.6K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.4K
Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
2.5K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K
Diversity of Protists II01:27

Diversity of Protists II

Alveolates are a group of organisms recognized by the presence of alveoli, which are cytoplasmic sacs located beneath the cell membrane. While their function remains uncertain, alveoli may help regulate water balance by controlling how much water enters and leaves the cell. In dinoflagellates, these structures may serve as armor plates. There are three major types of alveolates: ciliates, which move using cilia; dinoflagellates, which use flagella for movement; and apicomplexans, which are...
174