Mining Deep Sea Sponges for Novel Antimicrobial Biologics

Abstract

Antimicrobial resistance is one of the greatest threats to modern day healthcare, with 1.27 million deaths globally attributable to AMR in 2019 alone, and that number is only predicted to increase. One of the most prominent issues is the lack of effective and new antimicrobials on the market to treat multidrug resistant infections. Therefore, investment and research within the area of biodiscovery is desperately needed. Within this thesis, the investigation of a relatively unexplored deep-sea sponge, Pheronema carpenteri, is carried out to assess its potential as a source of novel antimicrobial compounds. Firstly, the microbiome was analysed using 16S rRNA amplicon sequencing, to see whether the microbiome contains species identified within literature with known antimicrobial capabilities, such as Streptomyces species. This indicated the presence of Proteobacteria, Actinobacteria and Crenarchaeota as the dominant species within this sponge. Then, a metabolomic approach was taken to see whether there are antimicrobials present in samples, without employing bacterial cultivation methods. There was a total of 83 unique molecules identified that could be further explored, with a number of various fatty acids present, with previous antimicrobial capability noted in literature. The second chapter involved the use of standard cultivation techniques and dilution to extinction (D:E) methods to generate culture collection of 389 bacteria, which were screened for antimicrobial activity against ESKAPE pathogens. A total of 72 isolates were identified with some level of narrow- or broad-spectrum activity. A One Strain MAny Compounds (OSMAC) approach was introduced at this stage to trigger bioactivity using a range of nutrient conditions and 12 isolates that were previously observed to be inactive were stimulated to produce antimicrobial activity. Finally, one bioactive Streptomyces strain was chosen for in-depth pursual of potential novel compounds. Culture dependent and independent methods were employed to analyse Biosynthetic Gene Clusters (BGCs) within the genome and facilitate prioritisation of four BGCs of interest (out of 40 in total in this strain) for future investigation. Culture methods involved the purification and identification of a potentially novel bioactive antimicrobial peptide with potent activity towards Gram-positive pathogens including MRSA and vancomycin resistant Enterococcus (VRE) and no toxicity in a Galleria mellonella model at concentrations well in excess of the antibacterial concentration.In this body of work, we evidence Pheronema carpenteri as a promising source of antimicrobial compounds. There are many uncultured Actinobacteriota species present within the microbiome that may harbour antimicrobial capabilities ideal for biodiscovery research.

Awarding Institution(s)

University of Plymouth

Supervisor

Kerry Howell, Mathew Upton

Document Type

Thesis

Publication Date

2025

Embargo Period

2026-09-23

Deposit Date

September 2025

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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This item is under embargo until 23 September 2026

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