Related Experiment Video

Updated: Jul 10, 2025

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract
07:42

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract

Published on: July 1, 2020

5.4K

Cytochrome c regulates hyphal morphogenesis by interfering with cAMP-PKA signaling in Candida albicans

Guisheng Zeng1, Xiaoli Xu1, Yee Jiun Kok2

  • 1A(∗)STAR Infectious Diseases Labs (A(∗)STAR ID Labs), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, #05-13 Immunos, Singapore 138648, Singapore.

Cell Reports
|November 19, 2023
PubMed

Insights

In Candida albicans, blocking lysine methylation of cytochrome c prevents hyphal growth. However, this unmethylated form accelerates proliferation, maintaining virulence in the fungal pathogen.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Invasive hyphal growth is a key virulence factor in the human fungal pathogen Candida albicans.
  • Understanding the regulation of hyphal development is crucial for combating fungal infections.

Purpose of the Study:

  • To investigate the role of CTM1 and lysine methylation in Candida albicans hyphal growth and virulence.
  • To elucidate the molecular mechanism by which cytochrome c methylation influences hyphal development and pathogenicity.

Main Methods:

  • Transposon-mediated genome-wide mutagenesis to identify genes affecting hyphal growth.
  • Transcriptomic analysis to assess gene expression changes in mutant strains.
  • Co-immunoprecipitation and in vitro kinase assays to study protein interactions and enzyme activity.

Main Results:

  • Inactivation of CTM1, a lysine methyltransferase, blocks hyphal growth by preventing trimethylation of cytochrome c (Cyc1) at K79.
  • Unmethylated Cyc1 suppresses hyphal growth by inhibiting cyclic AMP-protein kinase A (cAMP-PKA) signaling, leading to increased NRG1 repressor levels.
  • Despite defects in hyphal formation, ctm1Δ/Δ and cyc1K79A mutants exhibit accelerated proliferation and retain virulence in a mouse model.

Conclusions:

  • Cytochrome c lysine methylation is a novel regulatory mechanism controlling Candida albicans growth and virulence.
  • Unmethylated Cyc1 plays a critical role in suppressing hyphal development but promotes proliferation, highlighting a complex interplay with virulence.
  • This study reveals a new biological function for lysine methylation on cytochrome c and its impact on fungal pathogenicity.
Keywords:
C. albicansCP: Microbiologycytochrome c methylationhyphal morphogenesismetabolic adaptationmitochondria

More Related Videos

Use of In Vivo Imaging to Screen for Morphogenesis Phenotypes in Candida albicans Mutant Strains During Active Infection in a Mammalian Host09:24

Use of In Vivo Imaging to Screen for Morphogenesis Phenotypes in Candida albicans Mutant Strains During Active Infection in a Mammalian Host

Published on: October 12, 2022

1.9K
Assay for Adhesion and Agar Invasion in S. cerevisiae04:36

Assay for Adhesion and Agar Invasion in S. cerevisiae

Published on: November 8, 2006

15.0K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.6K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
Global Regulatory Systems01:28

Global Regulatory Systems

Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
28
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.5K