ArticleInfection and immunity2011
Discovery of a role for Hsp82 in Histoplasma virulence through a quantitative screen for macrophage lethality.
Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 39 citations in OpenAlex.
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- Revealing pathogenesis-associated metabolites inmSystems · 2025Article
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- Genotypic diversity, virulence, and molecular genetic tools inMicrobiology and molecular biology reviews : MMBR · 2024Review
- Insights on Covid-19 with superimposed pulmonary histoplasmosis: The possible nexus.Immunity, inflammation and disease · 2023Review
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- Histoplasma capsulatum Relies on Tryptophan Biosynthesis To Proliferate within the Macrophage Phagosome.Infection and immunity · 2023Article
- Caspofungin Affects Extracellular Vesicle Production and Cargo inJournal of fungi (Basel, Switzerland) · 2022Article
- Mac1-Dependent Copper Sensing PromotesmBio · 2022Article
- Key thermally dimorphic fungal pathogens: shaping host immunity.Open biology · 2022Review
- Immunoproteomic and Immunopeptidomic Analyses ofFrontiers in immunology · 2021Article
- Article
- Characterization of the APSES-family transcriptional regulators of Histoplasma capsulatum.FEMS yeast research · 2018Article
- Macrophage activation by IFN-γ triggers restriction of phagosomal copper from intracellular pathogens.PLoS pathogens · 2018Article
- Regulation of the heat shock transcription factor Hsf1 in fungi: implications for temperature-dependent virulence traits.FEMS yeast research · 2018Review
- O-Mannosylation of Proteins EnablesmBio · 2018Article
- Heat Shock Proteins in Histoplasma and Paracoccidioides.Clinical and vaccine immunology : CVI · 2017Review
- A silver bullet in a golden age of functional genomics: the impact ofFungal biology and biotechnology · 2017Review
- Revisiting old friends: Developments in understanding Histoplasma capsulatum pathogenesis.Journal of microbiology (Seoul, Korea) · 2016Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The application of forward genetics can reveal new factors required for the virulence of intracellular pathogens. To facilitate such virulence screens, we developed macrophage cell lines with which the number of intact host cells following infection with intracellular pathogens can be rapidly and easily ascertained through the expression of a constitutive lacZ transgene. Using known virulence mutants of Francisella novicida and Histoplasma capsulatum, we confirmed the applicability of these host cells for the quantitative assessment of bacterial and fungal virulence, respectively. To identify new genes required for Histoplasma virulence, we employed these transgenic macrophage cells to screen a collection of individual transfer DNA (T-DNA) insertion mutants. Among the mutants showing decreased virulence in macrophages, we identified an insertion in the locus encoding the Histoplasma Hsp82 homolog. The lesion caused by the T-DNA insertion localizes to the promoter region, resulting in significantly decreased HSP82 expression. Reduced HSP82 expression markedly attenuates the virulence of Histoplasma yeast in vivo. While the HSP82 hypomorph grows normally in vitro at 37°C and under acid and salinity stresses, its ability to recover from high-temperature stress is impaired. These results provide genetic proof of the role of stress chaperones in the virulence of a thermally dimorphic fungal pathogen.
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