Study examines population genomics in Cryptococcus neoformans

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Collaborative research has identified genomic variation in Cryptococcus neoformans that, although a result of environmental pressure, that may contribute to disease severity.

C. neoformans causes an estimated 1 million cases and 625,000 deaths worldwide each year, particularly burdening immunocompromised patients. This opportunistic pathogen is acquired environmentally, and cannot be transmitted from human to human.

This study, published recently in Genome Research, hoped to determine how selective pressures from the environment may have coincidentally adapted C. neoformans for human virulence.

The team sequenced 387 environmental and clinical isolates of C. neoformans, primarily sourced from sub-Saharan Africa, where the burden of this fungi is high. They discovered approximately 1 million variants across the samples and could easily distinguish between the three main lineages of C. neoformans – VNI, VNII and VNB.

In addition to this, the researchers also identified two subgroups of the VNB lineage termed VNBI and VNBII, which had been previously suggested. The team carried out large scale phenotypic profiling, discovering that VNBII were primarily clinical isolates and had associated genomic variants, for example, this group was less pigmented than others – a trait that normally protects against environmental stress.

A genome-wide association study highlighted some variants specifically associated with clinical isolates, including variants in virulence factors.  The findings demonstrate the evolutionary interplay between adaptation to natural environments and virulence, which is unique to opportunistic infections.

Author Christina Cuomo (Broad Institute, MA, USA) concluded: “Our work begins to examine how natural variation contributes to differences in human infection and suggests that some genetic pathways are less important during human infection than for growth in the environment.”

Sources: Deshardins CA, Giamberardino C Sykes SM et al. Population genomics and the evolution of virulence in the fungal pathogen Cryptococcus neoformans. Genome Res. doi:10.1101/gr.218727.11 (Epub ahead of print) (2017); www.eurekalert.org/pub_releases/2017-06/cshl-fgr060717.php

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