Population structure of human-infecting and environmental isolates of Coccidioides immitis, the fungus causing Valley fever

Coccidioides is a soil-dwelling fungus that can cause serious disease (coccidioidomycosis or Valley fever) when its spores are inhaled. Limiting exposure to environmental spores is critical for disease prevention, yet how Coccidioides is distributed in the soil and where people become exposed remain almost entirely unknown. Here we report the first genomes of environmental isolates of C. immitis, from sampling of rodent burrows in the highly endemic region--California's San Joaquin Valley. We sequenced 16 soil-derived isolates alongside 26 novel patient-derived isolates collected from the same region to investigate genetic structure and diversity in C. immitis, and the potential origins of human infection. We found evidence of regional population structure among environmental C. immitis strains, though with extensive allele sharing between clusters. Most patient isolates derived nearly 100% of their ancestry from a genetic cluster shared with soil isolates, suggesting that the Coccidioides strain inhaled by a human host represents a random draw from the environmental pathogen pool. Further, we found that high levels of genomic diversity in environmental C. immitis are partitioned into effectively clonal lineages within individual rodent burrows, with isolates from neighboring burrows differing by over 13,000 SNPs. Together, these data support a picture of diverse, regionally structured environmental populations of C. immitis, suggesting that strategies to assign patient exposures to general regions within the San Joaquin Valley may be possible.