Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms

• Published in: Cell reports physical science Vol. 5; no. 3; p. 101869
• Main Authors: De los Santos, Laura, Beckman, Robert L., DeBarro, Christina, Keener, James E., Torres, Marcelo D.T., Fuente-Nunez, Cesar de la, Brodbelt, Jennifer S., Fleeman, Renee M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-03-2024
• Subjects: antimicrobial peptide; bacterial resistance; biofilm; extracellular polysaccharide; Klebsiella pneumoniae; polyproline peptide; extracellular polysaccharide; antimicrobial peptide; polyproline peptide; bacterial resistance; Klebsiella pneumoniae; biofilm
• ISSN: 2666-3864; 2666-3864
• DOI: 10.1016/j.xcrp.2024.101869

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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•Confocal imaging visualizes the released cells and collapse of the biofilm matrix•Truncated analogs reveal polysaccharide interactions drive the matrix disruption•Mass spectrometry describes the polysaccharide interaction region of bac7 (1–35)•Topical application using a skin abscess model decreases the bacterial burden in vivo
De los Santos et al. use confocal microscopy to study biofilm matrix collapse by the defense peptide bac7 (1–35). The polysaccharide interactions of bac7 (1–35) cause the release of the biofilm cells and collapse of hypervirulent Klebsiella pneumoniae biofilms.