Should we really be using one strain to generalize an entire species? Having spent my PhD studying bacterial pathogens, I often observed that isolates of the same species varied greatly in their virulence strategies, the diseases they caused and the genes encoded in their genomes. Therefore, my answer was no. However, at the time I entered the world of fungal pathogenesis as a postdoctoral researcher, the concept of intraspecies heterogeneity had still not gained significant traction. Most researchers used a single ‘wild type’ reference strain to study their favourite pathogen. As a result, I was excited when Robert Cramer’s team clearly demonstrated the relevance of the intraspecies heterogeneity in Aspergillus fumigatus for its virulence. This work sparked my own research, which currently involves the characterization of A. fumigatus genomic diversity, revealing a tremendous amount of genomic heterogeneity underpinning its phenotypic heterogeneity.
A. fumigatus is a ubiquitous filamentous fungus that lives naturally in the soil. As an opportunistic pathogen, it can cause invasive pneumonia in immunocompromised individuals, contributing to an estimated 1.8 million deaths each year. Most researchers studying this pathogen use one of two wild-type reference strains called AF293 and CEA10. Kowalski, Beattie et al. demonstrated that these two strains have significant phenotypic differences in traits relevant to infection. Despite both strains being wild type, CEA10 was more fit under hypoxic growth in vitro. It was also significantly more lethal in a mouse model of infection, in part due to its ability to better invade lung tissue relative to AF293, which remained in the large airways. The authors extended their in vitro and in vivo analyses to a panel of environmental and clinical isolates of A. fumigatus, and they observed that the isolates presented a wide range of fitness under hypoxic stress, as well as variable lethality in a mouse model, mirroring what they observed with AF293 and CEA10 strains. Moreover, the authors observed that higher fitness in hypoxia was associated with shorter median survival times in the mouse. As a final demonstration of the role of hypoxic fitness in A. fumigatus virulence, the authors took the less virulent AF293 strain and experimentally evolved it under hypoxia. Strikingly, after 20 generations the strain exhibited significantly increased fitness under hypoxic conditions and virulence in the mouse model. The evolved strain now behaved more like CEA10, exhibiting more tissue invasion and higher mortality than the ancestor.
This is a preview of subscription content, access via your institution