Novel agents with inhibitory activity against the Burkholderia cepacia complex

• Main Author: Langley, Ross John
• Format: Dissertation
• Language: English
• Published: University of Edinburgh 2005

The purpose of these studies was to investigate novel antimicrobial agents against the Bcc, in particular, but also other problematic and emerging CF pathogens, including multiresistant epidemic P. aeruginosa strains, methicillin resistant S. aureus (MRSA), and Sten. maltophilia. The studies were based on three themes: First, the natural antimicrobial properties of honey: second, the lytic properties of bacteriophage and their associated lytic enzymes; third, the antimicrobial properties of novel mammalian cationic β-defensins. The studies were able to use a large collection of bacterial isolates held in the Edinburgh strain repository, including clinical, environmental and epidemic strains. In the case of the Bcc, resistance to the major families was shown to vary across the Bcc. In general, clinical isolates were more resistant to conventional antibiotics than environmental isolates. The results show that resistance against antimicrobial agents varies within the Bcc. NZMh exerts a promising bactericidal effect on members of the Bcc, including B. cenocepacia J2315. The novel Bcc bacteriophages may prove to be a useful panel for further study, either as vectors for horizontal gene transfer or as therapeutic agents. The results conform previous reports showing that Bcc isolates are inherently resistant to CAMPs, including the novel 5-cysteine defensin, Defrl. However, synthetic Defr1 was shown to be active against a panel of multiresistant pathogens associated with infections in CF. Further research is required to optimise the recombinant expression of Bcep781 endolysin, D3 lysin, and Defr1, to allow investigation of their antimicrobial properties and their potential as therapeutics agents against multiresistant CF pathogens.