Significance: The capsule of Klebsiella pneumoniae is composed of extracellular polysaccharides that inhibit the activity of host defense peptides and polymyxins. We generated an active antimicrobial peptide from a previously inactive parental peptide and characterized the interactions of these peptides with K. pneumoniae and its capsule. Compared with the inactive parent peptide, we found that our active peptide retained strong binding to capsule but lost structural integrity. These interactions induced capsule aggregation and capsule disruption, a previously undescribed mechanism for promoting antimicrobial activity toward K. pneumoniae . This finding may allow further exploitation of this mechanism to destroy the protective capsule that K. pneumoniae uses to resist our immune response and antibiotics.
1 January 2016 in European Journal of Medicinal Chemistry
A new rearranged spongian diterpene, darwinolide, has been isolated from the Antarctic Dendroceratid sponge Dendrilla membranosa. Characterized on the basis of spectroscopic and crystallographic analysis, the central seven-membered ring is hypothesized to originate from a ring-expansion of a spongian precursor. Darwinolide displays 4-fold selectivity against the biofilm phase of methicillin-resistant Staphylococcus aureus compared to the planktonic phase and may provide a scaffold for the development of therapeutics for this difficult to treat infection.