Understanding germination and pathogenicity in zygomycota species through genomic and transcriptomic approaches

Sephton Clark, Poppy (2019). Understanding germination and pathogenicity in zygomycota species through genomic and transcriptomic approaches. University of Birmingham. Ph.D.

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Abstract

Mucorales spores are the causative agents of the emerging disease mucormycosis. Mucorales species are also responsible for high quantities of food spoilage annually. The mechanism by which Mucorales spores cause disease and rot relies upon spore germination, however the mechanism underlying germination in these species remains poorly understood. Presented here are results which characterise Mucorales spore germination, through phenotypic and transcriptional studies (RNA-Seq), which followed the defined germination phenotype throughout. Hallmark pathways are identified through analysis of differentially expressed genes and co-transcriptional networks, providing targets for germination inhibition. With the resulting transcriptional data, the genome of Rhizopus delemar was enriched and analysed, thus providing better information on the Mucoralean genome. Comparative genomics was also employed to better understand genotypic variation between Mucorales species. To examine the differences in pathogenicity between species, and assess the impact of germination stage on pathogenicity, the transcriptional profile (RNA-Seq) of selected Mucorales species was examined upon phagocytosis by innate immune cells. To better understand the corresponding host response, the transcriptional response (single cell RNA-Seq) of innate immune cells to Mucorales infection was also examined. Finally, germination targets identified through the described analyses were targeted with suspected inhibitors to confirm function in germination regulation. This work has furthered our basic understanding of germination in these ancient fungi, indicated pathways essential to the germination programme of Mucorales species, and demonstrated a crucial role played by many of these pathways in host-fungal interactions of the Mucorales.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):