Huzefa Raja (@huzefaraj.bsky.social)

mSphere of Influence: Population-level thinking to unravel microbial pathogenicity | mSphere Fungal pathogens pose a serious and growing threat to human health. A striking feature of these organisms is their high interspecies phenotypic heterogeneity, which is underpinned by exceptionally dynamic and plastic genomes. For the WHO priority pathogen Aspergillus fumigatus, this includes notable variation between strains in gene content, stress resistance, induction of host responses, and virulence in animal models. Notably, most human fungal pathogens, including A. fumigatus, have evolved from non-pathogenic ancestors and therefore remain closely related to non-pathogenic relatives. The study “Strain heterogeneity in a non-pathogenic Aspergillus fungus highlights factors associated with virulence” (1) by Antonis Rokas’ group addresses the key research questions of whether these closely related non-pathogen relatives also possess a substantial degree of interspecific heterogeneity, and to what extent does their phenotypic variation overlaps with that of the pathogenic species, particularly under infection-relevant conditions? Strikingly, the authors find that Aspergillus fischeri, a close non-pathogenic relative of A. fumigatus, displays even greater intraspecific diversity and that this variation frequently overlaps with the pathogenicity-associated phenotypes of A. fumigatus. This study challenges the prevailing practice of categorizing the entire species as “pathogens” or “non-pathogens,” which is often based on research conducted using a single reference strain. Instead, it introduces a population-based framework, where the intraspecific diversity of pathogens and closely related species is defined across a diverse set of strains. This approach allows us to learn not only how these organisms cause disease but also how their virulence evolves. https://journals.asm.org/doi/10.1128/msphere.00588-24