Imperial College London
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Professor Matthew Fisher

Faculty of Medicine, School of Public Health

Professor of Fungal Disease Epidemiology
 
 
 
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Contact

 

matthew.fisher Website

 
 
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Location

 

1113Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Farrer:2018:10.1128/mSphere.00445-18,
author = {Farrer, RA and Ford, CB and Rhodes, J and Delorey, T and May, RC and Fisher, MC and Cloutman-Green, E and Balloux, F and Cuomo, CA},
doi = {10.1128/mSphere.00445-18},
journal = {mSphere},
title = {Transcriptional Heterogeneity of Cryptococcus gattii VGII Compared with Non-VGII Lineages Underpins Key Pathogenicity Pathways.},
url = {http://dx.doi.org/10.1128/mSphere.00445-18},
volume = {3},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cryptococcus gattii is a pathogenic yeast of humans and other animals which causes disease predominantly in immunocompetent hosts. Infection begins when aerosolized yeast or spores enter the body, triggering an immune response, including engulfment by macrophages. To understand the early transcriptional signals in both the yeast and its mammalian host, we performed a time-course dual-transcriptome sequencing (RNA-seq) experiment for four lineages of C. gattii (lineages VGI to IV) interacting with mouse macrophages at 1, 3, and 6 h postinfection. Comparisons of in vitro to ex vivo gene expression levels indicated that lineage VGII is transcriptionally divergent from non-VGII lineages, including differential expression of genes involved in capsule synthesis, capsule attachment, and ergosterol production. Several paralogous genes demonstrated subfunctionalization between lineages, including upregulation of capsule biosynthesis-related gene CAP2 and downregulation of CAP1 in VGIII. Isolates also compensate for lineage-specific gene losses by overexpression of genetically similar paralogs, including overexpression of capsule gene CAS3 in VGIV, which have lost the CAS31 gene. Differential expression of one in five C. gattii genes was detected following coincubation with mouse macrophages; all isolates showed high induction of oxidative-reduction functions and downregulation of capsule attachment genes. We also found that VGII switches expression of two laccase paralogs (from LAC1 to LAC2) during coincubation of macrophages. Finally, we found that mouse macrophages respond to all four lineages of C. gattii by upregulating FosB/Jun/Egr1 regulatory proteins at early time points. This report highlights the evolutionary breadth of expression profiles among the lineages of C. gattii and the diversity of transcriptional responses at this host-pathogen interface.IMPORTANCE The transcriptional profiles of related pathogens and their responses to host-induced stresses underp
AU  - Farrer,RA
AU  - Ford,CB
AU  - Rhodes,J
AU  - Delorey,T
AU  - May,RC
AU  - Fisher,MC
AU  - Cloutman-Green,E
AU  - Balloux,F
AU  - Cuomo,CA
DO  - 10.1128/mSphere.00445-18
PY  - 2018///
TI  - Transcriptional Heterogeneity of Cryptococcus gattii VGII Compared with Non-VGII Lineages Underpins Key Pathogenicity Pathways.
T2  - mSphere
UR  - http://dx.doi.org/10.1128/mSphere.00445-18
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30355668
VL  - 3
ER  -
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