Defining principles that influence antimicrobial peptide activity against capsulated Klebsiella pneumoniae

Abstract

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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Oct 21, 2020
Source ID
10.1073/pnas.2007036117

Entities

People

  • Bryan W Davies
  • Jennifer S. Brodbelt
  • Luis A. Macias
  • Renee M Fleeman

Organizations

  • Defense Threat Reduction Agency
  • National Institutes of Health
  • Robert A. Welch Foundation
  • University of Texas at Austin

Tags

Fields of Study

  • Biology

Readers

  • Microbial Pathology
  • Molecular and Cellular Biochemistry