ENGINEERING POLYMERIC ARTIFICIAL CELLULAR ENVIROMENTS (PACES) FOR ADHESION AND QUORUM SENSING

Lead Research Organisation: University of Birmingham
Department Name: Sch of Biosciences

Abstract

V. cholerae is the causative agent of cholera, a disease that affects 3-5 million people and causes 100,000-130,000 deaths/year. V. cholerae uses QS to control pathogenicity and the expression of virulence factors. Unlike many other pathogens, V. cholerae uses QS to repress virulence traits such as toxin production and host attachment. This way the pathogen coordinates host decolonization and environmental dissemination following infection. Small molecules designed to agonize QS result in repression of these virulence factors, compromising the ability of V. cholerae to colonise the host and cause acute diarrheal disease. However, this comes at the expense of increasing the ability of V. cholerae to spread to other hosts, compromising containment of the disease. It is therefore desirable to develop agents that inhibit the expression of the virulence factors while containing the pathogen, through clustering, and facilitating its mechanical removal from contaminated water, for instance. But to do this, we need to develop an understanding of how chemical functionality and material properties (e.g. molecular mass) affect the microbiology of the pathogen. In particular, we are interested in identifying how these materials properties can modulate the expression of relevant V. cholerae phenotypes, including those associated with virulence.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1644140 Studentship BB/M01116X/1 05/10/2015 30/09/2019 Oliver Creese
 
Description Initially cationic polymers were found to cluster and enhance quorum sensing in Vibrio cholerae which resulted in the following publication (doi: 10.1021/acschembio.8b00815). Next, poly(acryloyl hydrazide) (PAH) was employed as a high throughput screening platform to efficiently identify new polymer functionalities through post-polymerisation modification focusing on V. cholerae adhesion and physiology. We reported in the journal Polymer Chemistry (doi.org/10.1039/C9PY01222B) an optimisation in the synthesis of PAH which afforded polymers at varying molecular weights to be produced with improved control over the molecular mass dispersity. PAH was then modified with a small library of cationic and hydrophobic aldehydes as well as sugars (glucose, mannose, galactose) to probe the ability of these materials to sequester V. cholerae: initial findings suggest that polymers functionalised with hydrophobic and cationic aldehydes, in particular, imidazole carboxaldehyde can afford materials with a high affinity to V. cholerae and can significantly sequester planktonic bacteria from liquid media. It was found that aggregating V. cholerae with PAH modified with imidazole side groups resulted in virulence genes being downregulated while biofilm genes were upregulated.
Exploitation Route Polymer synthesis and biological protocols have now been established and will pave the way for further higher throughput screening of potential chemistries.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://pubs.rsc.org/en/content/articlelanding/2019/py/c9py01222b#!divAbstract