Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms

De los Santos, Laura; Beckman, IV, Robert L.; DeBarro, Christina; Keener, James E.; Torres, Marcelo D.T.; Fuente-Nunez, Cesar la; Brodbelt, Jennifer S.; Fleeman, Renee M.

doi:10.1016/j.xcrp.2024.101869

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Title: Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms

Journal Article · 12 March 2024 · Cell Reports Physical Science

DOI: https://doi.org/10.1016/j.xcrp.2024.101869 · OSTI ID:2530383

De los Santos, Laura ^[1]; Beckman, IV, Robert L. ^[1]; DeBarro, Christina ^[1]; Keener, James E. ^[2]; Torres, Marcelo D.T. ^[3]; Fuente-Nunez, Cesar la ^[3]; Brodbelt, Jennifer S. ^[2];

^[1]

University of Central Florida, Orlando, FL (United States)
University of Texas at Austin, TX (United States)
University of Pennsylvania, Philadelphia, PA (United States)

Hypervirulent Klebsiella pneumoniae is known for its increased extracellular polysaccharide production. Biofilm matrices of hyper- virulent 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 poly- saccharides 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 spec- trometry 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 bacte- rial burden. These findings unveil the potential of bac7 (1–35) poly- saccharide interactions to collapse K. pneumoniae biofilms.

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Research Organization:: University of Georgia, Athens, GA (United States)

Sponsoring Organization:: National Institute of General Medical Sciences of the National Institutes of Health; USDOE

Grant/Contract Number:: SC0015662

OSTI ID:: 2530383

Journal Information:: Cell Reports Physical Science, Journal Name: Cell Reports Physical Science Journal Issue: 3 Vol. 5; ISSN 2666-3864

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
Klebsiella pneumoniae
antimicrobial peptide
bacterial resistance
biofilm
extracellular polysaccharide
polyproline peptide

Title: Polyproline peptide targets Klebsiella pneumoniae polysaccharides to collapse biofilms

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