Tracing histoplasmosis genomic epidemiology and species occurrence across the USA

<p>Histoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of <i>Histoplasma capsulatum sensu lato</i>, <i>Histoplasma mississippiense</i> (Nam1) and <i>H. ohiense</i> (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 <i>Histoplasma</i> isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, <i>H. ohiense</i> and <i>H. mississippiense</i>; with sporadic cases caused by <i>H. suramericanum</i> in California and Texas. While <i>H. ohiense</i> is prevalent in eastern states, <i>H. mississipiense</i> was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that <i>H. ohiense</i> thrives in places with warmer and drier conditions, while <i>H. mississippiense</i> is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.</p>