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Published on: March 23, 2019
'Division of labour' in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak
Kerstin Voelz1, Simon A Johnston2, Leanne M Smith3
11] Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, West Midlands, Birmingham B15 2TT, UK [2] National Institute of Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham B15 2TH, UK.
Abstract:
Cryptococcus gattii is an emerging intracellular pathogen and the cause of the largest primary outbreak of a life-threatening fungal disease in a healthy population. Outbreak strains share a unique mitochondrial gene expression profile and an increased ability to tubularize their mitochondria within host macrophages. However, the underlying mechanism that causes this lineage of C. gattii to be virulent in immunocompetent individuals remains unexplained. Here we show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighbouring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. Thus, host reactive oxygen species, an essential component of the innate immune response, act as major signalling molecules to trigger a 'division of labour' in the intracellular fungal population, leading to increased pathogenesis within this outbreak lineage.
Insights
Host reactive oxygen species trigger Cryptococcus gattii to divide labor, enhancing fungal growth and pathogenesis within macrophages. This discovery explains the virulence of this emerging fungal pathogen in healthy individuals.
Area of Science:
- Mycology
- Immunology
- Cell Biology
Background:
- Cryptococcus gattii is an emerging pathogen causing outbreaks in healthy populations.
- Virulent strains exhibit unique mitochondrial gene expression and tubularization within macrophages.
- The mechanism for virulence in immunocompetent hosts remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which Cryptococcus gattii achieves virulence in immunocompetent hosts.
- To investigate the role of host reactive oxygen species in intracellular fungal adaptation.
Main Methods:
- Microscopy to observe fungal mitochondrial morphology within host macrophages.
- Analysis of fungal-host interactions under conditions mimicking innate immune responses.
Main Results:
- A subpopulation of intracellular C. gattii adopts tubular mitochondrial morphology in response to host reactive oxygen species (ROS).
- These ROS-induced tubular fungal cells promote the growth of non-tubular C. gattii cells.
- This division of labor facilitates pathogen establishment within the macrophage niche.
Conclusions:
- Host ROS act as signaling molecules, inducing a specialized fungal subpopulation.
- This ROS-mediated 'division of labor' enhances Cryptococcus gattii pathogenesis.
- The findings explain the increased virulence of this outbreak lineage in immunocompetent individuals.
