ArticleMolecular microbiology2015
Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H. capsulatum infection.
Article in Molecular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Macrophage phagocytosis ofmBio · 2026Article
- The Rpd3 histone deacetylase is a critical regulator of temperature-mediated morphogenesis and virulence in the human fungal pathogen Histoplasma.PLoS biology · 2026Article
- Rapid gain and loss of a chromosome drives key morphology and virulence phenotypes in the fungal pathogen Histoplasma.PLoS biology · 2026Article
- How Histoplasma Evades the Human Immune System.Acta medica academica · 2025Review
- Article
- Genomic epidemiology ofmBio · 2025Article
- Genotypic diversity, virulence, and molecular genetic tools inMicrobiology and molecular biology reviews : MMBR · 2024Review
- Common virulence factors betweenCurrent research in microbial sciences · 2024Review
- A Legionella toxin exhibits tRNA mimicry and glycosyl transferase activity to target the translation machinery and trigger a ribotoxic stress response.Nature cell biology · 2023Article
- Pathogenicity & virulence ofVirulence · 2022Review
- Genome-scale CRISPR screening reveals that C3aR signaling is critical for rapid capture of fungi by macrophages.PLoS pathogens · 2022Article
- Cbp1, a fungal virulence factor under positive selection, forms an effector complex that drives macrophage lysis.PLoS pathogens · 2022Article
- An Indian lineage of Histoplasma with strong signatures of differentiation and selection.Fungal genetics and biology : FG & B · 2022Article
- Drk1, a Dimorphism Histidine Kinase, Contributes to Morphology, Virulence, and Stress Adaptation inJournal of fungi (Basel, Switzerland) · 2021Article
- Kinase Inhibitor Library Screening Identifies the Cancer Therapeutic Sorafenib and Structurally Similar Compounds as Strong Inhibitors of the Fungal PathogenAntibiotics (Basel, Switzerland) · 2021Article
- BiodiversemSphere · 2020Article
- Turning on virulence: Mechanisms that underpin the morphologic transition and pathogenicity ofVirulence · 2019Review
- Sensing the heat and the host: Virulence determinants ofVirulence · 2019Review
- Opposing signaling pathways regulate morphology in response to temperature in the fungal pathogen Histoplasma capsulatum.PLoS biology · 2019Article
- How Environmental Fungi Cause a Range of Clinical Outcomes in Susceptible Hosts.Journal of molecular biology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Microbial pathogens induce or inhibit death of host cells during infection, with significant consequences for virulence and disease progression. Death of an infected host cell can either facilitate release and dissemination of intracellular pathogens or promote pathogen clearance. Histoplasma capsulatum is an intracellular fungal pathogen that replicates robustly within macrophages and triggers macrophage lysis by unknown means. To identify H. capsulatum effectors of macrophage lysis, we performed a genetic screen and discovered three mutants that grew to wild-type levels within macrophages but failed to elicit host-cell death. Each mutant was defective in production of the previously identified secreted protein Cbp1 (calcium-binding protein 1), whose role in intracellular growth had not been fully investigated. We found that Cbp1 was dispensable for high levels of intracellular growth but required to elicit a unique transcriptional signature in macrophages, including genes whose induction was previously associated with endoplasmic reticulum stress and host-cell death. Additionally, Cbp1 was required for activation of cell-death caspases-3/7, and macrophage death during H. capsulatum infection was dependent on the pro-apoptotic proteins Bax and Bak. Taken together, these findings strongly suggest that the ability of Cbp1 to actively program host-cell death is an essential step in H. capsulatum pathogenesis.
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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.