Role of glucose in the expression of Cryptococcus neoformans antiphagocytic protein 1, App1

Virginia Williams1, Maurizio Del Poeta

  • 1Department of Biochemistry & Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.

Eukaryotic Cell
|January 18, 2011
PubMed

Insights

Antiphagocytic protein 1 (App1) in Cryptococcus neoformans is upregulated in low-glucose environments like the lungs. This adaptation enhances fungal virulence by increasing App1 expression through transcription and mRNA stability.

Area of Science:

  • Medical Mycology
  • Molecular Biology
  • Infectious Diseases

Background:

  • Cryptococcus neoformans causes life-threatening meningoencephalitis in immunocompromised individuals.
  • The cryptococcus-specific protein antiphagocytic protein 1 (App1) is crucial for fungal virulence, regulating phagocytosis via complement receptors (CR), specifically CR3.
  • Glucose availability significantly impacts C. neoformans gene expression and virulence.

Purpose of the Study:

  • To investigate the role of glucose availability in regulating App1 expression in C. neoformans.
  • To understand how C. neoformans adapts to low-glucose environments, such as the mammalian lung.

Main Methods:

  • Culturing C. neoformans under varying glucose conditions.
  • Incubating C. neoformans in low-glucose biological fluids (BAL fluid, serum, cerebrospinal fluid).
  • Analyzing App1 expression at both transcriptional and mRNA stability levels.

Main Results:

  • App1 expression was dramatically upregulated under low-glucose conditions.
  • App1 was also upregulated when C. neoformans was incubated in low-glucose biological fluids.
  • App1 upregulation occurred through both increased transcription and enhanced mRNA stability.

Conclusions:

  • Glucose starvation is a key regulator of App1 expression in C. neoformans.
  • C. neoformans adapts to low-glucose environments by increasing App1 expression, potentially enhancing virulence.
  • These findings offer new insights into C. neoformans pathogenesis and adaptation strategies.

Related Concept Videos

Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
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,...
Glucose Homeostasis: Regulation of Blood Glucose01:02

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are co-secreted in...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...