UCF Burnett School of Biomedical Sciences
The Fleeman Lab
Investigating drug resistant bacteria to provide insight for developing novel post-antibiotic era therapeutics
Research Focus
Bacterial resistance to antibiotics has been on the rise while no new therapeutics have been introduced. As we enter a post-antibiotic era it is imperative we identify novel therapeutic approaches. The overall goal of our research is to understand the mechanisms bacteria use to resist both antimicrobials and the host immune system to guide therapeutic development for the post-antibiotic era. Identifying and developing adjuvant therapeutics to sensitize drug resistant bacteria to obsolete antibiotics or the host immune system can increase the therapeutic outcome of patients.
The current focus of the lab is examining the interactions of antimicrobial peptides with extracellular polysaccharides produced by bacteria K. pneumoniae. We have discovered that antimicrobial peptides can disrupt the capsule of K. pneumoniae and polyproline peptides are uniquely suited for this mechanism. We are working to reveal the therapeutic consequences of capsule disruption. We are also investigating the how capsule is regulated during biofilm formation as well as its contribution to the matrix polysaccharide composition.
Latest Publications
Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms
Hypervirulent Klebsiella pneumoniae is known for its increased extracellular polysaccharide production. Biofilms matrices of hypervirulent K. pneumoniae have increased polysaccharide abundance and are uniquely susceptible to disruption by peptide bac7 (1-35). Here, using confocal microscopy, we show that polysaccharides within the biofilm matrix collapse following bac7 (1-35) treatment. This collapse led to the release of cells from the biofilm, which were then killed by the peptide. Characterization of truncated peptide analogs revealed that their interactions with polysaccharide were responsible for the biofilm matrix changes that accompany bac7 (1-35) treatment. Ultraviolet photodissociation (UVPD) mass spectrometry with the parental peptide or a truncated analog bac7 (10-35) reveal the important regions for bac7 (1-35) complexing with polysaccharides. Finally, we tested bac7 (1-35) using a murine skin abscess model and observed a significant decrease in the bacterial burden. These findings unveil the potential of bac7 (1-35) polysaccharide interactions to collapse K. pneumoniae biofilms.
