Thesis
Investigating the host defence peptide, LL-37, as an antimicrobial : a Raman microscopic approach
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2023
- Thesis identifier
- T16512
- Person Identifier (Local)
- 201771945
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Society greatly relies on antibiotics which enable surgeries and treatments such as organ transplants and dialysis. However, The World Health Organisation (WHO) predicted antibiotic resistance could cause 10 million cases by 2050 if nothing is done. Bacteria can overcome the typically highly specific, slow-acting mechanisms of antibiotics by point mutation of target genes and horizontal gene transfer of genetic material between bacteria, for example. Alternatively, bacteria can increase antibiotic tolerance 10- to 1000-fold by growing biofilms: a community of bacterial colonies encased in a matrix of polymeric substances. The increased resistance is poorly understood, making biofilms difficult to treat. Thus, preventative antibiofilms are attractive therapeutics. Host defence peptides (HDP) are conserved within the immune system of all organisms. Resistance against them is thought to be low, due to their rapid, non-specific antimicrobial properties, and further immunomodulatory properties in vertebrates, making them attractive antibiotic alternatives. Moreover, they can reduce biofilm growth at sub-inhibitory concentrations. LL-37, known for modulating the human immune system and as an antimicrobial, is an excellent antibiofilm, but how this is achieved is unclear. Researching these properties, and biofilm growth in general, is challenging, often relying on destructive techniques or multiplexing chemical dyes to capture the full properties of the biofilm. Furthermore, HDPs are limited by their instability in serum. The overall aim of this research was to explore the non-destructive, label-free Raman microscopy in anti-biofilm research and the use of gold nanoparticles (AuNP) as a drug delivery mechanism to improve HDP stability. Both Raman spectroscopy coupled with chemometric analysis and stimulated Raman scattering (SRS) microscopy were good at capturing the subtle changes daily of an Escherichia coli (E. coli) biofilm. Furthermore, SRS showed that initial treatment of sub-inhibitory LL-37 delayed biofilm development. AuNPs were functionalise with LL-37 using several different methods. However, determining their efficacy against planktonic E. coli proved challenging. Growth inhibition was observed after 24 h treatment s This work showed Raman microscopy as an excellent technique for guiding antibiofilm research. However, further work is required to develop AuNP as a drug delivery mechanism for LL-37.
- Advisor / supervisor
- Davidson, Donald
- Faulds, Karen
- Graham, Duncan (Professor of Chemistry)
- Resource Type
- DOI
- Date Created
- 2022
- Embargo Note
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