Related Experiment Video

Updated: May 11, 2026

Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
08:52

Live-cell Video Microscopy of Fungal Pathogen Phagocytosis

Published on: January 9, 2013

Host iron withholding demands siderophore utilization for Candida glabrata to survive macrophage killing

Tracy Nevitt1, Dennis J Thiele

  • 1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America.

Plos Pathogens
|March 30, 2011
PubMed

Insights

Candida glabrata uses the Sit1 transporter for iron acquisition, crucial for surviving macrophage attacks. Host iron levels significantly impact fungal survival during infections, highlighting iron status as a disease modifier.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Host-Pathogen Interactions

Background:

  • Candida glabrata is an emerging opportunistic fungal pathogen causing severe infections, particularly in immunocompromised individuals.
  • Iron acquisition is a key virulence factor for microbial pathogens, and host iron dysregulation (deficiency or overload) affects infection outcomes.
  • The role of host iron status in modulating Candida glabrata pathogenesis remains largely unexplored.

Purpose of the Study:

  • To identify the primary siderophore-iron transporter in Candida glabrata.
  • To investigate the role of siderophore-mediated iron uptake in fungal survival against host immune responses, specifically macrophage killing.
  • To determine if host iron status influences Candida glabrata's susceptibility to macrophage-mediated clearance.

Main Methods:

  • Genetic deletion and complementation of the Sit1 gene in Candida glabrata.
  • In vitro assays assessing fungal survival and growth under iron-limited and iron-replete conditions.
  • Macrophage infection models, including those mimicking human iron overload conditions, to evaluate fungal resistance to killing.

Main Results:

  • Sit1 was identified as the sole siderophore-iron transporter essential for C. glabrata's virulence.
  • Siderophore-mediated iron acquisition via Sit1 is critical for C. glabrata's survival against macrophage microbicidal activities.
  • The fungal Sit1 transporter possesses a conserved extracellular SIderophore Transporter Domain (SITD) crucial for resisting macrophage killing.
  • C. glabrata senses and responds to altered host iron levels within macrophages, with Sit1-mediated survival being dependent on macrophage iron status.

Conclusions:

  • Host iron status is a significant modifier of infectious disease progression, influencing the reliance on specific microbial iron acquisition mechanisms.
  • Targeting the Sit1 transporter or manipulating host iron levels could represent novel therapeutic strategies against Candida glabrata infections.

More Related Videos

Establishment of an In vitro System to Study Intracellular Behavior of Candida glabrata in Human THP-1 Macrophages13:47

Establishment of an In vitro System to Study Intracellular Behavior of Candida glabrata in Human THP-1 Macrophages

Published on: December 11, 2013

Viability Assay of Trichoderma stromaticum Conidia Inside Human Peripheral Blood Mononuclear-Derived Macrophages07:21

Viability Assay of Trichoderma stromaticum Conidia Inside Human Peripheral Blood Mononuclear-Derived Macrophages

Published on: October 20, 2023

Related Concept Videos

Antimicrobial Proteins01:23

Antimicrobial Proteins

Antimicrobial proteins are important components of the immune system. They aid the body in combating pathogens by either killing them directly or hindering their replication processes. Four main types of antimicrobial substances are interferons, the complement system, iron-binding proteins, and antimicrobial proteins.
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Defense Against Bacterial Pathogens01:31

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Microbial Nutrition01:28

Microbial Nutrition

Organisms exhibit remarkable metabolic diversity, categorized based on how they acquire energy and carbon. These strategies enable survival in various ecological niches and are essential for maintaining energy flow and nutrient cycling within ecosystems.Energy and Carbon SourcesOrganisms are classified as phototrophs or chemotrophs based on energy acquisition. Phototrophs use light as their energy source, while chemotrophs rely on oxidizing chemical compounds. Further differentiation arises...
Fungal Phylum Microsporidia01:28

Fungal Phylum Microsporidia

Microsporidia are a group of obligate intracellular fungi that were initially classified as protists but were later reclassified based on phylogenetic, molecular, and structural evidence linking them to the Chytridiomycota. These unicellular, non-motile organisms are highly specialized parasites that infect a wide range of animal hosts, including humans. They have evolved extensive genomic and metabolic reductions, making them highly dependent on their hosts for survival.Morphology and Genomic...
Microbes and Other Elemental Cycles01:24

Microbes and Other Elemental Cycles

Microbial activity plays a pivotal role in the biogeochemical cycling of iron and manganese, especially at the redox gradients characteristic of stratified aquatic environments. These cycles are driven by microbial transformations between oxidized and reduced forms of the metals, allowing organisms to exploit them for metabolic energy and structural purposes.Iron Cycling Across Redox GradientsIn neutral, oxygen-rich surface waters, iron is predominantly found in its oxidized, insoluble ferric...
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...