- 10:00: Trial lecture. The subject of the trial lecture will be announced 10 working days before the lecture is given.
- 12:00: Public defence
The ordinary opponents are:
- First opponent: Professor Hanne Mørck Nielsen, University of Copenhagen, Denmark
- Second opponent: Professor Ole Andreas Økstad, University of Oslo, Norway
- Leader of the committee: Vice dean for research and innovation Kaare Magne Nielsen, OsloMet
The leader of the public defense is Professor Cecilie Ullstrøm Johannessen Landmark, OsloMet.
The main supervisor is Associate Professor Sanko Nguyen, OsloMet. The co-supervisor is Professor Colin Charnock, OsloMet.
Thesis abstract
Biofilms are structured communities of microorganisms embedded within a self-produced extracellular matrix. Biofilm-associated infections are difficult to treat, as the extracellular matrix acts as both a physical and chemical barrier that hinders the penetration of antimicrobial agents.
Treatment challenges are further compounded by the emergence of antimicrobial resistant strains. Together, these factors highlight the urgent need for novel antimicrobial agents suitable for clinical use, as well as effective delivery systems capable of targeting microbes within the biofilm.
Antimicrobial peptides (AMPs) offer a promising alternative due to their diverse mechanisms of action and ability to target drug-resistant microbes. However, their clinical application is hindered by suboptimal physicochemical and pharmacokinetic properties.
This thesis explores the antimicrobial and antibiofilm activity of novel AMPs, namely teixobactin analogues and micrococcin P1 (MP1), and liposomal encapsulation as a strategy to enhance their delivery and efficacy against biofilm-forming pathogens.
Initially, cholesterol-free fusogenic liposomes with varying surface charges were developed, and their ability to fuse with microbial cells and penetrate the biofilm matrix was assessed. All liposomal formulations demonstrated fusion with different microbial cells, highlighting their potential for AMP delivery.
Moreover, cationic liposomes showed the strongest interaction and retention within biofilms. Subsequently, MP1 was incorporated into cholesterol-free fusogenic liposomes formulated using phospholipids with varying acyl chain lengths. Liposomes with longest acyl chains exhibited higher MP1 entrapment efficiency and enhanced the peptide’s antimicrobial and antibiofilm activity.
Furthermore, MP1-loaded liposomes effectively disrupted Staphylococcus aureus biofilms formed on biomedical surfaces.
Finally, this thesis evaluated the antimicrobial and antibiofilm activities of three teixobactin analogues. The natural teixobactin compound represents a novel class of antibiotics with a unique mechanism of action and has attracted considerable interest as a potential drug candidate.
While all three analogues demonstrated promising efficacy against biofilm-forming pathogens, one showed comparatively stronger effects and is proposed as a lead candidate for further liposomal encapsulation.
In conclusion, this work highlights the potential of fusogenic liposomes as an advanced delivery system for novel AMPs targeting biofilms, offering a promising strategy for combating biofilm-associated infections.
