ArticleThe Journal of infectious diseases2022
Aspergillus Utilizes Extracellular Heme as an Iron Source During Invasive Pneumonia, Driving Infection Severity.
Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Optimal production of Phanerochaete chrysosporium manganese peroxidases and Trametes sp. C30 laccase hybrid Lac131 in Aspergillus niger for lignin bioconversion.Biotechnology for biofuels and bioproducts · 2025Article
- Review
- Essential role of hepcidin in host resistance to disseminated candidiasis.Cell reports · 2025Article
- The heme scavenger hemopexin protects against lung injury during aspergillosis by mitigating release of neutrophil extracellular traps.JCI insight · 2025Article
- Hemorrhages and risk factors in patients undergoing thromboprophylaxis in a respiratory critical care unit: a secondary data analysis of a cohort study.Journal of intensive care · 2024Article
- New developments in Aspergillus fumigatus and host reactive oxygen species responses.Current opinion in microbiology · 2024Review
- NLRC5 senses NADCell · 2024Article
- Characterization ofJournal of medical microbiology · 2024Article
- NIAID/SMB Workshop on Multiscale Modeling of Infectious and Immune-Mediated Diseases.Bulletin of mathematical biology · 2024Article
- Heme sensing and trafficking in fungi.Fungal biology reviews · 2023Article
- Computational Modeling of Macrophage Iron Sequestration during Host Defense against Aspergillus.mSphere · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDepriving microbes of iron is critical to host defense. Hemeproteins, the largest source of iron within vertebrates, are abundant in infected tissues in aspergillosis due to hemorrhage, but Aspergillus species have been thought to lack heme import mechanisms. We hypothesized that heme provides iron to Aspergillus during invasive pneumonia, thereby worsening the outcomes of the infection.
methodsWe assessed the effect of heme on fungal phenotype in various in vitro conditions and in a neutropenic mouse model of invasive pulmonary aspergillosis.
resultsIn mice with neutropenic invasive aspergillosis, we found a progressive and compartmentalized increase in lung heme iron. Fungal cells cultured under low iron conditions took up heme, resulting in increased fungal iron content, resolution of iron starvation, increased conidiation, and enhanced resistance to oxidative stress. Intrapulmonary administration of heme to mice with neutropenic invasive aspergillosis resulted in markedly increased lung fungal burden, lung injury, and mortality, whereas administration of heme analogs or heme with killed Aspergillus did not. Finally, infection caused by fungal germlings cultured in the presence of heme resulted in a more severe infection.
conclusionsInvasive aspergillosis induces local hemolysis in infected tissues, thereby supplying heme iron to the fungus, leading to lethal infection.
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