Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms
Authors:
Laura De los Santos 1, Robert L. Beckman IV 1, Christina DeBarro 1, James E. Keener 2, Marcelo D.T. Torres 3 4 5 6, Cesar de la Fuente-Nunez 3 4 5 6, Jennifer S. Brodbelt 2, Renee M. Fleeman 1 7 8
Affiliation:
1 Division of Immunity and Pathogenesis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA
2 Department of Chemistry, The University of Texas at Austin, Austin, TX 78712, USA
3 Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4 Departments of Bioengineering and Chemical and Biomolecular Engineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA 19104, USA
5 Department of Chemistry, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA
6 Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA
Description:
Hypervirulent Klebsiella pneumoniae is known for its increased extracellular polysaccharide production. Biofilm matrices of hypervirulent K. pneumoniae have increased polysaccharide abundance and are uniquely susceptible to disruption by peptide bactenecin 7 (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 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.
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