Poster Presentation Australian Society for Medical Research Annual Scientific Meeting 2016

Interfering with Adhesion of Klebsiella pneumoniae to Host Collagen - A strategy for Design of Novel Agents to Fight Infections (#141)

Anna E Lohning 1
  1. Bond University, Robina, QLD, Australia

Hospital-acquired infections are often associated with the opportunistic pathogen, Klebsiella pneumonia, resulting in urinary tract infections, pneumonia, septicaemia etc. As for other key pathogens, the emergence of antibiotic resistant strains is a world-wide concern. Colonization in respiratory and urinary epithelia is facilitated by Type 1 or Type 3 fimbrial appendages. Type 3 fimbriae are characterized by their ability to agglutinate tannic acid-treated erythrocytes1 but are capable of binding to a wide variety of substrata of biotic and abiotic origin. The MrkD adhesin mediates binding to extracellular matrix collagen though allelic mutants of MrkD show different binding specificities. Recently the structure of the plasmid borne MrkD1P’s receptor binding domain was solved shedding light on the nature of the binding interaction.2 Two distinct regions were identified, the polar pocket and hydrophobic patch. Despite this, in vivo interactions between the adhesins and collagen are yet to be elucidated. While the MrkD1P (plasmid) adhesin are frequently expressed in Klebsiella oxytoca, the chromosomal proteins, MrkD1C1 and MrkD1C2, predominate in K. pneumonia, most common in the community. We used homology modelling to explore features that may explain differences in their binding specificities. Additionally triple-helical collagen fragments were constructed to investigate protein-protein interactions important for adhesion. Techniques used to probe the interactions included molecular docking and molecular dynamics simulations using GROMACS software for simulation of biological systems. Results from the study to date have shown that despite a relatively high degree of sequence homology between the two chromosomal species, differences in the manner in which they interact with the collagen fragments were observed which may explain the binding affinity differences.  This data can be exploited in the design of peptide-like compounds with potential use as anti-adhesive agents to prevent of minimise infections from the organism.

  1. 1. Huang YJ, Wu CC, Chen MC, Fung CP, Peng H, Biochem Biophys Res Commun, 2006, 350(3), 537-42
  2. 2. Rêgo, Ana Toste, Johnson, Jeremiah.G., Geibel, Sebastian, Enguita, F.J., Clegg, Steven and Waksman, Gabriel, Molecular Microbiology, 2012, 86(s4), 882-893.