Date of Award

3-10-2025

Document Type

Doctoral Thesis

Degree Name

Doctor of Philosophy

First Advisor

Dr. Craig Murphy

Second Advisor

Dr. Eamonn Culligan

Abstract

Marine-derived compounds are promising candidates in the search for new antimicrobials. This thesis explores their potential against a suite of clinically relevant bacterial strains. Saltwater environments were screened for antimicrobial compounds, leading to the identification of two lead bacterial strains, Bacillus subtilis_MTUA2 and Bacillus velezensis_MTUC2. Cell-free supernatant (CFS) of these strains significantly reduced the growth of MRSA and clinical S. aureus isolates (50%), inhibited biofilms by 99% and 90%, respectively, and reduced E. coli biofilms by 90%. To expand the scope of bioactive marine sources, crude extracts from two seaweeds, Codium fragile and Fucus vesiculosus, obtained using methanol and water were evaluated for additional properties such as antioxidant potential. F. vesiculosus methanol extracts demonstrated the highest phenolic and protein content, with strong antioxidant activity. F. vesiculosus methanol and water extracts exhibited potent antimicrobial activity, particularly against Gram-positive bacteria, achieving MBIC50 with 0.78% against S. aureus. Conversely, C. fragile extracts exhibited a broader antibiofilm effect, although at higher concentrations. Building on these findings, synergistic effects of the identified bacterial CFS and extracts were assessed in combination with conventional antibiotics. For selected bacterial strains, combinations enhanced susceptibility, suggesting potential for adjunctive use. Stability tests showed that both CFS and extracts retained antimicrobial activity under varied salt (3-10%), temperature (4-90 °C), and pH (4-10) conditions, with methanol extracts proving more robust. The bioavailability and safety profiles of these compounds were subsequently tested to assess their potential clinical applicability. Simulated intestinal fluid exposure, protein-binding studies, and in vitro cytotoxicity testing were also performed. These evaluations indicated their pharmacological characteristics and supported their suitability for further development. Overall, these findings contribute to the growing body of research on marine-derived antimicrobials and support their potential use in addressing antimicrobial resistance.

Access Level

info:eu-repo/semantics/openAccess

Download

Share

COinS