Macquarie University
01whole.pdf (2.8 MB)
Download file

Uncovering the glycan-mediated host-pathogen interactions in cystic fibrosis

Download (2.8 MB)
posted on 2022-11-09, 05:33 authored by Prapti ChakrabortyPrapti Chakraborty

Pseudomonas aeruginosa is a prevalent pathogen in cystic fibrosis (CF) lungs with elaborate defence mechanisms serving to counter the host immune response. This thesis hypothesises a previously unstudied defence mechanism involving a P. aeruginosa lectin (LecB) that proposedly acts to neutralise host microbicidal glycoproteins. Multi-pronged approaches involving methods in microbiology and biochemistry were employed to produce robust structural and functional data supporting the hypothesis by firstly showing the binding of LecB to the N-glycans of human neutrophil elastase (HNE) and, importantly, that LecB fully neutralises the potent microbicidal activity of HNE against P. aeruginosa. In-silico 3D structure analyses indicated spatial compatibility and bivalent binding between two neighbouring carbohydrate binding domains (CBDs) of tetrameric LecB and two HNE N-glycans. Moreover, complete LecB sequence conservation from genotypically/phenotypically diverse clinical P. aeruginosa strains was identified suggesting essential roles of LecB. Excitingly, a LecB-mediated inhibition of the HNE enzyme activity easily disrupted with D-mannose was shown. Finally, advanced mass spectrometry supported the existence of a LecB-HNE complex. This thesis has generated novel data suggesting that P. aeruginosa LecB carry out other roles than acting as the glue in biofilms by proposing a completely new pathogen defence mechanism involving LecB-mediated neutralisation of host microbicidal glycoproteins.


Table of Contents

1. Introduction and aims -- 2. Materials and Methods -- 3. Results -- 4. Discussion -- 5. Conclusions and future directions -- 6. References -- 7. Appendices


A thesis submitted to Macquarie University for the Master of Research degree

Awarding Institution

Macquarie University

Degree Type

Thesis MRes


Thesis (MRes), Macquarie University, Faculty of Science and Engineering, 2022

Department, Centre or School

Department of Molecular Sciences

Year of Award


Principal Supervisor

Morten Thaysen-Andersen

Additional Supervisor 1

Anahit Penesyan


Copyright: Prapti Chakraborty Copyright disclaimer:




72 pages

Usage metrics

    Macquarie University Theses