bioRxiv Science⌕ Search

Biology subjects

Christensen, K. E.

Publications and source records attributed to Christensen, K. E..

5 recordsLinked to original sources

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↗

Coconut filters woven using Native Hawaiian techniques capture coastal microplastic and sunscreen pollution and support fungal bioremediation

Microplastic pollution and sunscreen contaminants increasingly threaten coastal ecosystems, yet many existing clean-up solutions rely on synthetic materials, creating additional carbon emissions during manufacturing, or address pollutant removal without subsequent treatment, leaving risk of future run-off back into the ocean. Here we evaluate coconut husk, an abundant and biodegradable agricultural byproduct, as a dual-function platform for physical pollutant capture and microbial bioremediation applications. To test the natural microbial community of coconuts for bioremediation potential, we isolated fungi from coconut husks and screened their growth under plastic- and sunscreen-containing conditions. 24 fungal isolates grew on plastic- and/or sunscreen media, with several isolates belonging to genera previously documented to degrade plastic, i.e. Chaetomium, Curvularia, Meyerozyma, Cladosporium, and Fusarium. We then developed filtration modules using coconut husks, fiber, and leaves, basing our design on traditional Hawaiian papale lau niu (coconut leaf hat) weaving. In filtration trials, the woven devices captured up to 76.58 +/- 3.73% of suspended microplastic particles in 2 minutes and captured suspended sunscreen with a 533.51 +/- 0.81 NTU decrease in net turbidity of the surrounding water than in control trials with no filter. Overall, this work introduces a form of natural innovation for pollution clean-up, building on coconut-based materials, traditional techniques, and microbial resilience to create a sustainable and cost-effective system.

microbiology↗

Evolutionary insights into an ancient fungal transition from land to sea

Though fungi have largely been studied in the context of terrestrial niches, aquatic species that originated from terrestrial ancestors can be found across the fungal kingdom. To date, the mechanisms of these transitions from land to sea have remained poorly understood, and it is unclear what traits are associated with the specialization of a fungal to marine environments. Here we develop Kluyveromyces budding yeasts, sampled from terrestrial, estuarine, and marine niches, as a model for the evolution of fungi into the ocean. Comparative analyses of genomes from the genus revealed a contraction in genome size and gene number in aquatic Kluyveromyces compared to their terrestrial relatives, including at genes annotated in alcoholic fermentation. In laboratory culture, we uncovered evidence for phenotypic losses in aquatic Kluyveromyces species, namely compromised desiccation and cold resistance relative to the terrestrial clade. Aquatic Kluyveromyces also exhibited better salt tolerance than terrestrial species, reflecting an evolutionary gain consonant with their provenance from seawater. Furthermore, in molecular-evolution analyses, we found robust signal for positive selection in the aquatic Kluyveromyces lineage, most notably at genes annotated in respiration. We interpret these results under a model in which the release of ethanol, which allows yeasts in terrestrial niches to kill off bacterial competitors at close range, has little use in the water; aquatic Kluyveromyces thus evolved to lose fermentation but gained other metabolic and stress-tolerance innovations essential for fitness in the marine niche. We propose that the syndrome of genomic features and phenotypes in aquatic Kluyveromyces reflects broadly relevant mechanisms of evolutionary transitions by fungi into ocean environments.

evolutionary biology↗

Dissecting an ancient stress resistance trait syndrome in the compost yeast Kluyveromyces marxianus

Organisms specialized to extreme environments can be the product of millions of years of evolutionary engineering and refinement. The underlying genetics can be quite distinct from the ones operating at earlier stages of trait innovation. In this work, we have developed the multi-stress resistant yeast Kluyveromyces marxianus, which diverged from its closest relative >20 million years ago, as a model for interspecies comparative biology and genomics. In growth assays of the Kluyveromyces genus, we found that K. marxianus exhibited unique tolerance of high heat and a subset of chemical stress conditions. We then generated and analyzed omic profiles from across the genus to find molecular features associated with- and potentially causal for - K. marxianus traits. Expression profiling revealed divergent lipid processing and membrane transport programs in K. marxianus, borne out in changes in lipid utilization in experimental assays. Sequence analyses found robust evidence for expansions in gene families in the K. marxianus genome, most notably among transmembrane transporters and in metabolic enzymes. In molecular-evolution tests, we identified adaptive protein variants throughout the K. marxianus genome among which plasma membrane transporters were over-represented. These data enable a model of the molecular mechanisms and evolutionary pressures underlying K. marxianus traits, including adaptive changes to transporters, lipid processing, and membrane functions mediating stress resistance. Significance statementMany traits of basic and applied interest arose long ago and manifest in the modern day as fixed in a given species; understanding how evolution built them, potentially over millions of years, remains a key challenge in the field. In this study, we report stress-resistance phenotypes that distinguish the yeast Kluyveromyces marxianus from its relatives, and we discover unique patterns of genetic and regulatory variation in membrane-protein genes, as well as unique properties of lipid metabolism, in this species. We propose a broadly applicable model in which evolution can tune membrane lipid composition and membrane-protein function to boost cellular fitness in challenging environments.

evolutionary biology↗

The 677C>T variant in methylenetetrahydrofolate reductase causes morphological and functional cerebrovascular deficits in mice

Vascular contributions to cognitive impairment and dementia (VCID) particularly Alzheimers disease and related dementias (ADRDs) are increasing; however, mechanisms driving cerebrovascular decline are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate and methionine cycles. Variants in MTHFR, notably 677C>T, are associated with dementias, but no mouse model existed to identify mechanisms by which MTHFR677C>T increases risk. Therefore, MODEL-AD created a novel knock-in (KI) strain carrying the Mthfr677C>T allele on the C57BL/6J background (Mthfr677C>T) to characterize morphology and function perturbed by the variant. Consistent with human clinical data, Mthfr677C>T mice have reduced enzyme activity in the liver and elevated plasma homocysteine levels. MTHFR enzyme activity as well as critical metabolites in the folate and methionine cycles are reduced in the Mthfr677C>T brain. Mice showed reduced tissue perfusion in numerous brain regions by PET/CT as well as significantly reduced vascular density and increased GFAP-expressing astrocytes in frontal cortex. Electron microscopy revealed cerebrovascular damage including endothelial and pericyte apoptosis, reduced luminal size, and increased astrocyte and microglial presence in the microenvironment. Collectively, these data suggest critical perturbations to cerebrovascular function in Mthfr677C>T mice supporting its use as a model for preclinical studies of VCID.

genetics↗