We are currently investigating the interactions of extracellular polysaccharides from K. pneumoniae with antimicrobial peptides. We have shown that capsule aggregation by antimicrobial peptides leads to disruption of the capsule layer protecting K. pneumoniae. The extracellular polysaccharides in the biofilm matrix are also potential targets of antimicrobial peptides as we have shown sensitivity of hypermucoviscous biofilms to the polyproline peptide Bac7 (1-35). Our research suggests polyproline antimicrobial peptides are particularly well suited to bind and aggregate with capsule polysaccharides and biofilm polysaccharides. We are now investigating the potential of natural polyproline peptides identified from pigs, cows, dolphins, and insects.

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We hypothesize that capsule disruption by antimicrobial peptides is a mechanism used by these host derived therapeutics to sensitize K. pneumoniae to the host immune system. We are currently studying the effects of polyprolines on the ability of K. pneumoniae to evade recognition by the host immune system and uptake by professional phagocytes. Additional work is being done to investigate the synergy of capsule disruption natural antimicrobial peptides with other antimicrobial peptides that are trapped by capsule unable to penetrate to the bacterial membrane target.

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Molecular characterization of capsule polysaccharide interactions with with antimicrobial peptides is ongoing and multifactorial combining a genetic surface screening platform and native mass spectrometry. The UVPD native mass spectrometry is part of a collaborative effort with Dr. Jennifer Brodbelt at UT Austin. We aim to reveal the the physical chemical properties and amino acids involved with capsule aggregation.