Biology subjects

Radosevich, M. T.

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

4 recordsLinked to original sources

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↗