Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms

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 micro...

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Bibliographic Details
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
Online Access:	Get full text
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Summary:	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. [Display omitted] •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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 AUTHOR CONTRIBUTIONS R.M.F. conceived the idea and designed the experimentation. The biofilm experiments were performed by R.M.F., L.D.l.S., R.L.B., and C.D. The UVPD native mass spectrometry work was performed and the data were processed by J.E.K. and J.S.B. C.D. produced the AlphaFold images and BioRender vectors. M.D.T.T. and C.d.l.F.-N. performed the HEK293T toxicity, blood lysis, and murine skin abscess infection, and collected and graphed the results. R.M.F. wrote the text and discussed the results with L.D.l.S. L.D.l.S., R.L.B., J.E.K., J.S.B., C.d.l.F.-N., and M.D.T.T. participated in manuscript editing for the final manuscript.
ISSN:	2666-3864 2666-3864
DOI:	10.1016/j.xcrp.2024.101869