ArticleInfection and immunity2014
Histoplasma capsulatum depends on de novo vitamin biosynthesis for intraphagosomal proliferation.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- How Histoplasma Evades the Human Immune System.Acta medica academica · 2025Review
- Elevated carbon dioxide enhances the growth and reduces the antifungal susceptibility ofMicrobiology spectrum · 2025Article
- Revealing pathogenesis-associated metabolites inmSystems · 2025Article
- Article
- Genotypic diversity, virulence, and molecular genetic tools inMicrobiology and molecular biology reviews : MMBR · 2024Review
- β-1,3-Glucan recognition byApplied and environmental microbiology · 2024Article
- Kicking sleepers out of bed: Macrophages promote reactivation of dormant Cryptococcus neoformans by extracellular vesicle release and non-lytic exocytosis.PLoS pathogens · 2023Article
- Article
- Targeted gene deletions in the dimorphic fungal pathogenmSphere · 2023Article
- Histoplasma capsulatum Relies on Tryptophan Biosynthesis To Proliferate within the Macrophage Phagosome.Infection and immunity · 2023Article
- Riboflavin Targets the Cellular Metabolic and Ribosomal Pathways of Candida albicansMicrobiology spectrum · 2023Article
- Comparative Genomics ofJournal of fungi (Basel, Switzerland) · 2023Article
- A putative terpene cyclase gene (Frontiers in microbiology · 2023Article
- Pathogenicity & virulence ofVirulence · 2022Review
- NIH4215: A mutation-prone thiamine auxotrophic clinicalFrontiers in fungal biology · 2022Article
- Riboflavin as a promising antimicrobial agent? A multi-perspective review.Current research in microbial sciences · 2022Review
- Review
- A metabolic inhibitor arms macrophages to kill intracellular fungal pathogens by manipulating zinc homeostasis.The Journal of clinical investigation · 2021Article
- Evasion of MAIT cell recognition by the AfricanProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
During infection of the mammalian host, Histoplasma capsulatum yeasts survive and reside within macrophages of the immune system. Whereas some intracellular pathogens escape into the host cytosol, Histoplasma yeasts remain within the macrophage phagosome. This intracellular Histoplasma-containing compartment imposes nutritional challenges for yeast growth and replication. We identified and annotated vitamin synthesis pathways encoded in the Histoplasma genome and confirmed by growth in minimal medium that Histoplasma yeasts can synthesize all essential vitamins with the exception of thiamine. Riboflavin, pantothenate, and biotin auxotrophs of Histoplasma were generated to probe whether these vitamins are available to intracellular yeasts. Disruption of the RIB2 gene (riboflavin biosynthesis) prevented growth and proliferation of yeasts in macrophages and severely attenuated Histoplasma virulence in a murine model of respiratory histoplasmosis. Rib2-deficient yeasts were not cleared from lung tissue but persisted, consistent with functional survival mechanisms but inability to replicate in vivo. In addition, depletion of Pan6 (pantothenate biosynthesis) but not Bio2 function (biotin synthesis) also impaired Histoplasma virulence. These results indicate that the Histoplasma-containing phagosome is limiting for riboflavin and pantothenate and that Histoplasma virulence requires de novo synthesis of these cofactor precursors. Since mammalian hosts do not rely on vitamin synthesis but instead acquire essential vitamins through diet, vitamin synthesis pathways represent druggable targets for therapeutics.
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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.