{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:40:37Z","timestamp":1787942437120,"version":"build-2784847793"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:00:00Z","timestamp":1540339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2018,10,31]]},"abstract":"<jats:p>\n                    The transcriptional profiles of related pathogens and their responses to host-induced stresses underpin their pathogenicity. Expression differences between related pathogens during host interaction can indicate when and how these genes contribute to virulence, ultimately informing new and improved treatment strategies for those diseases. In this paper, we compare the transcriptional profiles of five isolates representing four lineages of\n                    <jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>\n                    in rich media. Our analyses identified key processes, including those involving cell capsule, ergosterol production, and melanin, that are differentially expressed between lineages, and we found that VGII has the most distinct profile in terms of numbers of differentially expressed genes. All lineages have also undergone subfunctionalization for several paralogs, including capsule biosynthesis and attachment genes. Most genes appeared downregulated during coincubation with macrophages, with the largest decrease observed for capsule attachment genes, which appeared to be coordinated with a stress response, as all lineages also upregulated oxidative stress response genes. Furthermore, VGII upregulated many genes that are linked to ergosterol biosynthesis and switched from expression of the laccase\n                    <jats:italic>LAC1<\/jats:italic>\n                    to expression of\n                    <jats:italic>LAC2 ex vivo<\/jats:italic>\n                    . Finally, we saw a pronounced increase in the FosB\/Jun\/Egr1 regulatory proteins at early time points in bone marrow-derived macrophages, marking a role in the host response to\n                    <jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>\n                    . This work highlights the dynamic roles of key\n                    <jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>\n                    virulence genes in response to macrophages.\n                  <\/jats:p>","DOI":"10.1128\/msphere.00445-18","type":"journal-article","created":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T10:37:58Z","timestamp":1540291078000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Transcriptional Heterogeneity of\n                    <i>Cryptococcus gattii<\/i>\n                    VGII Compared with Non-VGII Lineages Underpins Key Pathogenicity Pathways"],"prefix":"10.1128","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-7458","authenticated-orcid":false,"given":"Rhys A.","family":"Farrer","sequence":"first","affiliation":[{"name":"MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom"},{"name":"Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"},{"name":"UCL Genetics Institute, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Ford","sequence":"additional","affiliation":[{"name":"Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-7860","authenticated-orcid":false,"given":"Johanna","family":"Rhodes","sequence":"additional","affiliation":[{"name":"MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United 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