Biology subjects

Radosevich, M. T.

Publications and source records attributed to Radosevich, M. T..

6 recordsLinked to original sources

bioRxiv2026

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.

ecology↗

bioRxiv2026

Urban soils along the Kern River and Los Gatos Creek are hotspots for Coccidioides in the San Joaquin Valley of California

Coccidioidomycosis (Valley fever) is acquired through inhalation of spores produced by fungi in the genus Coccidioides. Coccidioides is commonly detected in, and cultivated from, the lung tissue of native rodents and the soils within their burrows. Coccidioidomycosis is acquired by exposure to environmentally produced spores and is not spread between hosts. Thus, determining the location of rodent burrows with soils harboring Coccidioides will be critical for understanding coccidioidomycosis incidence and modelling how Coccidioides distributions will be affected by global change. Coccidioides is readily detected in rodent burrows on undisturbed land, has not been detected on agricultural land, and is unstudied on urban land. To test the hypothesis that Coccidioides is in urban soil, we sampled rodent burrow soils from the banks of two water ways, the Kern River and Los Gatos Creek, which transect two cities, Bakersfield and Coalinga, in the San Joaquin Valley of California. To test the hypothesis that Coccidioides would not be detected at higher elevations, we extended our sampling of rodent burrows along waterways into the mountains of California. From 1178 soil and settled dust samples, we find that Coccidioides is found in urban riparian environments in Bakersfield and Coalinga, on riparian land on the floor of the San Joaquin Valley but not at higher elevations and is negatively correlated with modeled soil moisture. Coccidioides shows significant co-occurrence patterns with animal-associated fungal taxa, but no broader relationships with the greater fungal community. Our results warrant caution when excavating urban rodent burrows in the region. Author SummaryCoccidioidomycosis, or Valley fever, is caused by a fungus that primarily infects people when its spores become airborne and are inhaled. Although the fungus is found in the burrows of rodents, its presence in cities has been unclear. We investigated whether urban environments in Californias San Joaquin Valley, an area with high Valley fever incidence, harbor the fungus. By sampling more than a thousand soils and settled dust samples along riparian areas (waterways and adjacent environments) in Bakersfield and Coalinga, we found that the fungus that causes Valley fever, Coccidioides, occurs in urban riparian zones. The fungus was restricted to low elevations and was more likely to be detected in drier soils. We also compared positive and negative soils using DNA-based surveys of fungi. While the broader fungal community showed no strong relationship to Coccidioides, several species tied to animal activity were more common in positive samples, supporting a link to rodent hosts. These findings show that urban waterways can serve as habitat for Coccidioides. Because these areas lie within major population centers, identifying and avoiding disturbance of rodent burrows may reduce exposure risk, and future models of Valley fever should account for riparian corridors and local ecological conditions.

microbiology↗

bioRxiv2024

Detection of airborne Coccidioides spores using lightweight portable air samplers affixed to uncrewed aircraft systems in California's Central Valley

Coccidioidomycosis is an emerging fungal infection caused by inhalation of Coccidioides spp. spores. While airborne dispersal is critical to Coccidioides transmission, limited recovery of the pathogen from air has hindered understanding of the aerosolization and transport of spores. Here, we examine uncrewed aircraft systems (UAS) with portable, active air samplers as a novel means of capturing aerosolized Coccidioides and characterizing emissions and exposure risk. We sampled in September 2023 in eastern San Luis Obispo County, California, in an area with confirmed Coccidioides immitis in soils. We completed 41 20-minute flights across 14 sites using UAS equipped with an 8 L/min bioaerosol sampler and a low-cost particulate matter sensor. We sampled source soils and air under ambient conditions using one UAS at 1-10 m above ground level, and under a simulated high-dust event using two UAS, one at <2 m height and one at 5-12 m. We detected Coccidioides DNA in two of 41 air samples (4.9%), both under ambient conditions at 8 m above ground level, representing the highest known height of airborne Coccidioides detection. Spatially explicit UAS-based sampling could enhance understanding of Coccidioides aerobiology and enable detection in hard-to-reach or hazardous air masses, including dust storms and wildfire smoke. SynopsisUAS-based air sampling for bioaerosols, including pathogenic Coccidioides spp., opens new possibilities for characterizing the aerosolization and transport of fungal spores and other airborne pathogens.

ecology↗

bioRxiv2024

Characterizing the soil microbial community associated with the fungal pathogen Coccidioides immitis

Coccidioidomycosis is a fungal disease affecting humans and other mammals, caused by environmental pathogens of the genus Coccidioides. Understanding the ecological factors that shape the distribution of Coccidioides in soils is important for minimizing the risk of human exposure, though this remains challenging due to the pathogens highly variable spatial distribution. Here, we examined associations between the soil microbial community and Coccidioides immitis presence within the Carrizo Plain National Monument--a minimally disturbed grassland ecosystem, and the site of a longitudinal study examining the effects of rodents and their burrows on C. immitis presence in soils. Using internal transcribed spacer 2 (ITS2) and 16S sequencing to characterize the soil fungal and bacterial communities, we found over 30 fungal species, including several other members of the Onygenales order, that co-occurred with Coccidioides more frequently than expected by chance. Coccidioides-positive samples were significantly higher in microbial diversity than negative samples, an association partly driven by higher Coccidioides presence within rodent burrows compared to surface soils. Soil source (i.e., rodent burrow versus surface soil) explained the largest amount of variation in bacterial and fungal community diversity and composition, with soils collected from rodent burrows having higher microbial diversity than those collected from adjacent surface soils. While prior evidence is mixed regarding associations between Coccidioides and microbial diversity, our study suggests that favorable microhabitats such as rodent burrows can lead to a positive association between soil diversity and Coccidioides presence, particularly in otherwise resource-limited natural environments.

ecology↗

bioRxiv2024

Small mammals and their burrows shape the distribution of Coccidioides in soils: a long-term ecological experiment

BackgroundFor nearly all human fungal pathogens, the environmental constraints on their distributions remain poorly understood, hindering disease management. Here, we investigated the role of zoonotic host presence, soil conditions, and their interaction on the presence of Coccidioides immitis - an emerging fungal pathogen and causative agent of coccidioidomycosis. MethodsA long-term experimental study initiated in 2007 in the Carrizo Plain National Monument, California excluded rodents from certain areas (20 by 20-meter exclosures; n = 20) via the installation of submerged mesh fences, leaving emptied burrows intact. We collected 1,988 soil samples over four sampling periods spanning April 2021 to April 2022 using a factorial design that crossed burrows and surface soils (i.e., top 10 cm of soil) with exclosures (i.e., rodent absence) and non-exclosures (i.e., rodent presence). We measured in situ soil moisture, temperature, and vegetation, and analyzed soils for C. immitis DNA. ResultsThe proportion of samples containing C. immitis was significantly higher (p <0.0001) in burrow samples taken from outside rodent exclosures (i.e., rodents present; 28.5% positive) compared to burrow samples taken from within exclosures (i.e., rodents absent; 19.7%), surface soils outside of exclosures (3.6%) and surface soils within exclosures (0.5%). In generalized linear mixed models adjusting for soil conditions, rodent presence, and sample type (burrow vs. surface soil), we estimated that the odds of detecting C. immitis were 19.2 (95% CI: 11.3 - 36.7, p < 0.0001) times higher in soils taken from burrows compared to surface soils, and 2.6 (95% CI: 1.0 - 5.6, p = 0.049) times higher in soils where rodents were present compared to absent. Soil moisture was the only abiotic factor associated with C. immitis detection (odds ratio per 1% increase in water content: 0.83, 95% CI: 0.70 - 0.89, p = 0.0002). In mediation analyses, we estimated that 73.7% (95% CI: 68.9, 78.5) of the total association between rodents and Coccidioides detection effect was attributable to rodent creation of burrows. ConclusionsRodent creation and occupation of burrows substantially increases C. immitis detection. Synergy between reservoir host presence and environmental conditions may exist for other human fungal pathogens.

ecology↗

bioRxiv2023

Engineered CD47 protects T cells for enhanced antitumor immunity

Adoptively transferred T cells and agents designed to block the CD47/SIRP axis are promising antitumor therapeutics, which activate distinct arms of the immune system. We administered anti-CD47 (CD47) with adoptively transferred T cells with the goal of enhancing antitumor efficacy but observed rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors, which blunted therapeutic benefit. CD47 mediated CAR T clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered a CD47 variant (47E) that engaged SIRP and provided a "dont-eat-me" signal that was not blocked by CD47 antibodies. TCR or CAR T cells expressing 47E were resistant to clearance by macrophages following CD47, and mediated significant, sustained macrophage recruitment into the TME. Although many of the recruited macrophages manifested an M2-like profile, the combined therapy resulted in synergistic enhancement in antitumor efficacy. This work identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T cell directed therapeutics with those designed to activate macrophages. It further delivers a therapeutic approach capable of simultaneously harnessing the antitumor effects of T cells and macrophages that manifests markedly enhanced potency against solid tumors.

bioengineering↗