Study of vancomycin derivatives on bio-conjugated activity and bio-optical imaging.
Date of Issue2012
School of Physical and Mathematical Sciences
The glycopeptide antibiotic vancomycin (Van) is usually served as a last resort to effectively treat methicillin-resistant Gram-positive bacterial infections. It acts through the specific binding affinity to the C- termini D-Ala-D-Ala motif of peptidoglycan, which inhibits the biosynthesis of bacterial cell wall and leads to cell death. However, with overuse of antibiotic in clinic and animal feeds, bacteria having resistance to vancomycin emerged as a serious threat to public health, such as vancomycin-resistant enterococci (VRE). Their termini peptide sequence is mutated from D-Ala-D-Ala to D-Ala-D-Lac, which results in around 1000-fold decrease in binding affinity to vancomycin. This research dissertation focuses on the study of vancomycin and its derivatives on molecular interaction, photodynamic antibacterial activity and bacterial Raman imaging. Chapter 2 describes the investigation of molecular interactions between vancomycin and bacterial cell wall analogs in various solutions based on fluorescence correlation spectroscopy (FCS) and molecular dynamic (MD) simulation. This study clearly demonstrates that the components constituting the buffer solution have a profoundly disturbing effect on the complex formed between low-affinity drug resistant bacterial cell peptide and vancomycin. These results facilitate the fully understanding of the structure and activity of vancomycin towards bacterial cell wall peptide analogs, which is significant to design novel drug candidates against drug-resistant bacterial strains.