Aspergillus

Iron Dependency and Siderophores#

Aspergillus species produce three major siderophore types for Iron acquisition.

TAFC (triacetylfusarinine C)—extracellular siderophore secreted to scavenge environmental iron; detectable in serum and urine as a biomarker of invasive aspergillosis.^{[1]Infection metallomics for critical care in the post-COVID eraPatil RH, Luptakova D, Havlicek V · 2021Open reference 1 ↓}

Ferricrocin—intracellular siderophore used for iron storage and distribution within hyphae. Coprogen—additional extracellular siderophore contributing to iron piracy from the host.

TAFC is detected in urine within 4.5 hours of inoculation in animal models, making it a faster diagnostic marker than galactomannan (the current clinical standard).^{[1]Infection metallomics for critical care in the post-COVID eraPatil RH, Luptakova D, Havlicek V · 2021Open reference 1 ↓}

Iron acquisition is essential for virulence: siderophore-deficient A. fumigatus mutants show dramatically attenuated pathogenicity, connecting iron availability directly to infection outcome. The host counters fungal iron piracy through Nutritional Immunity (Metal Sequestration) mechanisms including Lactoferrin and transferrin sequestration.

Role in the Mycobiome#

Part of the normal gut and respiratory mycobiome at low abundance; becomes pathogenic under immunosuppression.

Elevated Aspergillus abundance in the gut mycobiome is reported in Multiple Sclerosis, where patients show higher fungal alpha diversity and increased Aspergillus alongside Saccharomyces.^{[2]The Microbiome-Gut-Brain Axis in Multiple SclerosisDusan Radojevic, Svetlana Sokovic Bajic, Miroslav Dinic et al. · 2023Open reference 2 ↓}

In the cancer mycobiome, Aspergillus species are detected in tumor tissues and may contribute to the tumor microenvironment through mycotoxin production and immune modulation.^{[3]The mycobiome in human cancer: analytical challenges, molecular mechanisms, and therapeutic implicationsTing Ding, Chang Liu, Zhengyu Li · 2025Open reference 3 ↓}

Invasive Aspergillosis#

Primarily affects immunocompromised patients: post-transplant, chemotherapy, prolonged corticosteroids, and critically ill ICU patients.^{[1]Infection metallomics for critical care in the post-COVID eraPatil RH, Luptakova D, Havlicek V · 2021Open reference 1 ↓}

COVID-19-associated pulmonary aspergillosis (CAPA) emerged as a significant complication, with 19.4% mortality in critically ill patients.^{[1]Infection metallomics for critical care in the post-COVID eraPatil RH, Luptakova D, Havlicek V · 2021Open reference 1 ↓[4]Patil 2021 — Infection Metallomics in the COVID EraPatil, A., Gholap et al. · 2021Open reference 4 ↓}

Diagnosis via siderophore detection (TAFC in serum/urine by LC-MS) represents a paradigm shift from culture-based methods to infection-metallomics-based approaches.^{[1]Infection metallomics for critical care in the post-COVID eraPatil RH, Luptakova D, Havlicek V · 2021Open reference 1 ↓}

Neurological Disease#

Anti-Aspergillus antibodies detected in CSF of MS patients, suggesting CNS fungal exposure may contribute to neuroinflammation.^{[5]A Fungal World: Could the Gut Mycobiome Be Involved in Neurological Disease?Jessica D. Forbes, Charles N. Bernstein, Helen Tremlett et al. · 2019Open reference 5 ↓} Elevated Aspergillus abundance in the gut mycobiome of MS patients alongside fungal alpha diversity increases.^{[2]The Microbiome-Gut-Brain Axis in Multiple SclerosisDusan Radojevic, Svetlana Sokovic Bajic, Miroslav Dinic et al. · 2023Open reference 2 ↓}

Key Metabolites#

TAFC / ferricrocin / coprogen—iron-chelating siderophores; diagnostic biomarkers. Gliotoxin—immunosuppressive mycotoxin produced by A. fumigatus; inhibits NF-kB and induces apoptosis in immune cells. Aflatoxins—carcinogenic mycotoxins produced primarily by A. flavus and A. parasiticus.