Biogeographical and phylogenetic boundaries of the specialised metabolism of pseudonocardia from marine origin

Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2022
Thesis identifier
  • T16345
Person Identifier (Local)
  • 201860240
Qualification Level
Qualification Name
Department, School or Faculty
  • Multidrug-resistant pathogens have become a global threat. In this context, filamentous actinomycetes have been proven to be an exceptional source of antimicrobial metabolites. In particular, rare actinomycetes isolated from marine environments have been proposed as a potential source of yet untapped specialised metabolites. In this study, two novel species, Pseudonocardia abyssalis sp. nov. and Pseudonocardia oceani sp. nov., isolated from deep Southern Ocean sediments are described, both in terms of their phenotypic and genomic characterization. Furthermore, the genomic architecture, with a focus on Biosynthetic Gene Clusters (BGC), across eight strains belonging to the two novel species was investigated. As a result, a total of 13 Gene Cluster Families (GCF) were identified, of which six GCFs comprise BGCs from both species, and one was annotated specifically of each species. Following genome analysis, a comparative mass-spectrometry based metabolomics analysis was carried out, including phylogenetically closely-related non-marine species, as well as other Pseudonocardia strains isolated from different marine environments. Then, genomics and metabolomics data were correlated through NPLinker, an unsupervised method for integrating paired omics data. As a result, it was demonstrated that the BGC evolution and distribution across strains is mainly shaped by phylogeny over any biogeographical pattern. Furthermore, metabolomics and genome mining tools were used to assess the role of the specialised metabolites on interactions between members of the Pseudonocardia genus isolated from different marine environments. To this end, using challenge bioassays, antagonist interaction between nine Pseudonocardia spp. isolated from marine sediments and two non-marine species was examined and correlated to the strains' phylogeny and their metabolomics profile. To understand the spatial dynamics, matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) was used to examine in situ species chemical interactions between the Southern Ocean strains and their closest relatives. This analysis showed that phylogeny is the main predictor of antagonistic interactions among free-living Pseudonocardia strains. Moreover, a group of parent ions produced by P. abyssalis were identified as possible metabolites involved in the inter species interactions. Overall, this work showcases the power of a combined genomics-metabolomics approach to investigate rare actinomycetes from understudied locations and have uncovered a wealth of both biosynthetic and chemical diversity for further investigation.
Advisor / supervisor
  • Duncan, Katherine
Resource Type