Caring about the future

FATE - Study of adaptive evolution events associated with the rise of pathogenic potential in Aspergillii colonising polluted soils
CESAM Responsible researcher - Artur Alves
Programme - COMPETE - Programa Operacional Competitividade e Internacionalização
Execution dates - 2021-03-31 - 2024-02-29 (35 Months)
Funding Entity - FCT - Fundação para a Ciência e a Tecnologia
Funding for CESAM - 36125 €
Total Funding - 249937.1 €
Proponent Institution - Universidade Nova de Lisboa
Participating Institutions
Universidade de Aveiro


Project Description
We will disclose “Why, How and What” leads to increase fungal virulence in polluted soils. Our planet is continuously being challenged and altered by both natural and anthropogenic factors. Among these, climate change is, perhaps, the most relevant and is believed to largely result from human activity. Chemical pollution and climate change cannot be dissociated. Climate change may lead to geological/geochemical or atmospheric alterations with severe consequences (e.g. global warming) that impact human lives. William D. Nordhaus was awarded with the Nobel Prize in Economics in 2018 for integrating climate change impacts into macro-economic analysis. Chemical pollutants are nowadays found ubiquitously at a global scale, affecting all ecosystems. Soil is a key reservoir of biological diversity on our planet; one of its major ecological, social and economic services. It ensures numerous ecosystem functions and plays major roles in surface water purification, in recycling of mineral elements (soil fertility), in carbon storage and in the mitigation of pollution. The economic profit derived from soil biodiversity has been estimated to be thousands of billions of dollars. Fungi are responsible worldwide for ca. 2 million human deaths annually. These numbers are expected to enlarge since the most vulnerable population - immune-compromised individuals – is also increasing at a fast pace. Fungi are proficient opportunistic pathogens, capable of colonising virtually all habitats on Earth and to survive extreme environments and scarcity of food resources. The increased burden of fungal infections in humans, emergence of azole-resistant fungi (e.g. Candida auris) and crosskingdom pathogens (phytopathogens that acquire capacity to infect animals) has been linked to many contributing factors, including climate change, but the link to soil pollution remains overlooked. Importantly, pollution has been demonstrated to contribute to the spread of antimicrobial resistance genes across some pathogenic bacteria. Inspired by these facts, we have been seeking to understand how pollution impacts soil mycobiota. Our team has demonstrated important defensive roles of mycobiota of soils contaminated with the persistent organic pollutant pentachlorophenol (PCP). The mycobiota ensured rapid decay of the pollutant but paid a high price since PCP exposure elicited pathogenic tradeoffs. These included dysregulation of C and N metabolisms, secretion of proteins associated with pathogenesis and decreased susceptibility to fungicides. FATE current-working hypothesis is that pollution acts, globally, as driver of increased pathogenicity in fungi. This may be a consequence of either fast adaptive evolution events or selective pressure towards virulent strains. We are particularly interested to understand if soil pollution favours the emergence of pathogenic aspergilli capable of infecting human hosts. This taxon includes species that are relevant human pathogens, e.g. A. fumigatus, and some that are opportunistic pathogens usually resistant to the fungicides commonly used in clinics, e.g. A. terreus. In addition, we are targeting three specific chlorinated pollutants: PCP –an archetypal chlorinated aromatic pollutant, diclofenac and triclosan, both classified as contaminants of emergent concern which are structurally related to PCP. We will analyse soils across two continents and characterise their mycobiota and pollution loads. Adaptive evolution experiments along exposure to pollution will be applied on aspergilli isolates to generate specialised-phenotypes. Functional and genomic assays will help to uncover potential specialisation events leading to virulence. Deep genome resequencing will be used to spot pathogenic trails (e.g. single-nucleotide-polymorphisms), some of which might have been mapped before in clinical aspergilli strains. The expertise acquired by our partnership over a decade of research on multidisciplinary aspects of environmental sciences, fungal biology, genomics and pathogenicity, analytics, and on the ecology of polluted soils, supports the feasibility of our complex and ambitious proposal. The datasets to be generated will allow us to answer: How does chemical pollution affects mycobiota communities globally? Are there specialisation trails associated with pathogenicity, common to all polluted locations? Is there a rise in pathogenic aspergilli as a result of chemical pollution? Which are the genomic features that define augmented virulence in environmental strains?




CESAM members on this project

Researcher

CESAM Funding: UIDP/50017/2020 + UIDB/50017/2020 + LA/P/0094/2020