ArticleMolecular microbiology2008
Histoplasma capsulatum secreted gamma-glutamyltransferase reduces iron by generating an efficient ferric reductant.
Article in Molecular microbiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Review
- Genotypic diversity, virulence, and molecular genetic tools inMicrobiology and molecular biology reviews : MMBR · 2024Review
- Iron Deprivation Modulates the Exoproteome inFrontiers in cellular and infection microbiology · 2022Article
- Ferric iron reductases and their contribution to unicellular ferrous iron uptake.Journal of inorganic biochemistry · 2021Review
- The "Little Iron Waltz": The Ternary Response ofJournal of fungi (Basel, Switzerland) · 2020Review
- Sensing the heat and the host: Virulence determinants ofVirulence · 2019Review
- Review
- Metals in fungal virulence.FEMS microbiology reviews · 2018Review
- Differentiation of the fungus Histoplasma capsulatum into a pathogen of phagocytes.Current opinion in microbiology · 2017Review
- The Fungal PathogenFrontiers in microbiology · 2017Article
- HcZrt2, a zinc responsive gene, is indispensable for the survival of Histoplasma capsulatum in vivo.Medical mycology · 2016Article
- Revisiting old friends: Developments in understanding Histoplasma capsulatum pathogenesis.Journal of microbiology (Seoul, Korea) · 2016Review
- Histoplasma capsulatum surmounts obstacles to intracellular pathogenesis.The FEBS journal · 2016Review
- Phytotoxin production in Aspergillus terreus is regulated by independent environmental signals.eLife · 2015Article
- Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis.PLoS pathogens · 2015Article
- Histoplasma capsulatum, lung infection and immunity.Future microbiology · 2015Review
- Glycosylation and immunoreactivity of the Histoplasma capsulatum Cfp4 yeast-phase exoantigen.Infection and immunity · 2014Article
- Metabolism in fungal pathogenesis.Cold Spring Harbor perspectives in medicine · 2014Review
- Histoplasma capsulatum depends on de novo vitamin biosynthesis for intraphagosomal proliferation.Infection and immunity · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The intracellular fungal pathogen Histoplasma capsulatum (Hc) resides in mammalian macrophages and causes respiratory and systemic disease. Iron limitation is an important host antimicrobial defence, and iron acquisition is critical for microbial pathogenesis. Hc displays several iron acquisition mechanisms, including secreted glutathione-dependent ferric reductase activity (GSH-FeR). We purified this enzyme from culture supernatant and identified a novel extracellular iron reduction strategy involving gamma-glutamyltransferase (Ggt1) activity. The 320 kDa complex was composed of glycosylated protein subunits of about 50 and 37 kDa. The purified enzyme exhibited gamma-glutamyl transfer activity as well as iron reduction activity in the presence of glutathione. We cloned and manipulated expression of the encoding gene. Overexpression or RNAi silencing affected both GGT and GSH-FeR activities concurrently. Enzyme inhibition experiments showed that the activity is complex and involves two reactions. First, Ggt1 initiates enzymatic breakdown of GSH by cleavage of the gamma-glutamyl bond and release of cysteinylglycine. Second, the thiol group of the released dipeptide reduces ferric to ferrous iron. A combination of kinetic properties of both reactions resulted in efficient iron reduction over a broad pH range. Our findings provide novel insight into Hc iron acquisition strategies and reveal a unique aspect of Ggt1 function in this dimorphic mycopathogen.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.