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کتابخانه
محل استقرار
TLpq2402549753
انگلیسی
Multi-Omic Data Mining to Elucidate Molecular Adaptation Mechanisms of Filamentous Fungi Exposed to Space Environment
[Thesis]
Blachowicz, Adriana
Wang, C. C. C.
University of Southern California
2019
232
Ph.D.
University of Southern California
2019
Filamentous fungi are dual organisms that can be both useful for mankind and threatening to human habitats and health. These omnipresent extremotolerant microorganisms are associated with a range of hostile environments and the human body. Immense adaptability to a variety of conditions enables fungi to thrive in what seems like inhospitable niches, including man-made closed habitats. One such habitat is the International Space Station (ISS), which is a research platform under strict microbiological scrutiny. Recent advances in the next generation sequencing technologies have transformed the scientists' approach to study fungal adaptation mechanisms. Insights into genome, proteome and metabolome allow for holistic assessment of changes in the molecular suite of fungi exposed to extreme conditions. In this work multi-omic approach was applied to study response of various filamentous fungi to space environment. We investigated both, unintentional fungal "hitchhikers" that unknowingly followed people and cargo aboard the ISS Aspergillus fumigatus (Chapter 2 and 3) and Aspergillus niger (Chapter 6 and 7), and fungi sent to the ISS in strictly controlled experiments, including several Chernobyl isolated fungi, ISS-isolated A. niger (Chapter 4 and 5), and Aspergillus nidulans (Chapter 8). Aspergillus fumigatus is a ubiquitous in nature saprophytic fungus that may pose a health hazard to immunocompromised individuals. Upon isolation from the ISS, during microbial observatory study, two A. fumigatus isolates were characterized to investigate space conditions-induced phenotype when compared to well-studied Af293 and clinical isolate CEA10. Initial analyses showed that genomic diversity of both ISS-isolates was within the genetic variance of 95 environmental and clinical isolates, however both ISS isolates showed increased virulence in larval zebrafish model of invasive aspergillosis (Chapter 2). Observed increase in virulence prompted further molecular analyses of ISS isolates. Proteome characterization revealed up-regulation of proteins involved in carbohydrate metabolism, secondary metabolism and stress responses in both ISS isolates when compared to clinical isolates. Among increased in abundance proteins were TpcK, TpcF and TpcA involved in trypacidin biosynthesis, Asp-hemolysin, AcuE and PdcA involved in glyoxylate cycle and ethanol fermentation, respectively (Chapter 3). A. niger, ubiquitous in built and natural environments fungus, which has known biotechnological applications was among ISS-isolated and further characterized strains. Proteomic analysis of ISS-isolated A. niger revealed altered abundance of proteins involved in carbohydrate metabolism, cell wall modulation, and oxidative stress response when compared to well-studied ATCC 1015. Similarly to A. fumigatus whole genome analysis revealed genetic variance within the diversity observed among other species in the A. niger/ welwitschiae/lacticoffeatus clade (Chapter 6). Further, secondary metabolite (SM) analysis showed significant increase in the yields of produced compounds, especially antioxidant Pyranonigrin A. Gene targeted deletion was used to determine gene cluster responsible for Pyranonigrin A production. Lastly, radiation protective potential of Pyranonigrin A against UV-C was tested (Chapter 7). To study fungal adaptation to space conditions in controlled experiments several Chernobyl- and ISS-isolated fungi were selected and characterized prior to space flight. Assessment of UV-C and simulated Mars conditions resistance revealed strain-dependent survival. Further, upon exposure to SMC two surviving strains A. fumigatus and Cladosporium cladosporoides showed induced production of SM and differential expression of proteins involved in translation, carbohydrate metabolism and energy conversion processes when compared to unexposed control strains (Chapter 4). Genomic characterization of ISS-grown A. niger revealed accumulation of SNPs within specific regions of the genome, while observed INDELs were distributed across all chromosomes. Proteome analysis showed differential expression of proteins involved in carbohydrate metabolism, and stress response, while SM characterization revealed that SM production is altered by space conditions (Chapter 5). Lastly, when fungal model organism A. nidulans and three mutant strains were grown aboard the ISS and compared to ground counterparts alterations in specific genome regions were observed. Additionally, proteins involved in carbohydrate metabolism and stress response were differentially expressed among the ISS-grown strains and alterations in SM yields were revealed (Chapter 8). This thesis underscores the significance of multi-omic characterization in comprehension of the fungal response to distinct environmental conditions. Such in depth analyses are imperative for elucidating plausible mechanisms of enhanced virulence of A. fumigatus and may unveil biotechnological applications of fungi during space explorations. Further, understanding of possible molecular alterations triggered by irradiation is crucial for the success of long-term manned space flights to ensure both astronauts' health and maintenance of the closed habitat.
Ecology
Blachowicz, Adriana
Wang, C. C. C.
مطالعه متن کتاب p
[Thesis]
276903
a
Y
