Defining principles that influence antimicrobial peptide activity against capsulated <i>Klebsiella pneumoniae</i>
Renee M. Fleeman, Luis A. Macias, Jennifer S. Brodbelt, Bryan W. Davies
Abstract
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.