The CpxP family of bacterial chaperones: novel antibiotic targets

Lead Research Organisation: University of East Anglia
Department Name: Biological Sciences

Abstract

"There is a particular lack of new agents to treat infections caused by multi-drug resistant (MDR) Gram-negative bacteria" was a major conclusion from a report by the European Centre for Disease Prevention in 2013. One reason for this is Gram-negative bacteria (GNB) possess an outer membrane (OM); making them impermeable and therefore resistant to many antibiotics that are active against Gram-positives. Infection by the bacterial pathogen, Salmonella is a global issue, with approximately 94 million people contracting gastroenteritis or food poisoning each year. Morbidity of Salmonella infections, particularly associated with outbreaks, is exacerbated by antibiotic resistance, which can lead to more complicated illness in patients. Novel therapeutic agents to treat Salmonella infections are urgently required. An exciting challenge is to decipher the genetic, molecular and biophysical basis of membrane impermeability as a bacterial resistance mechanism. This could expand the use of therapeutic compounds to include those to which Salmonella are currently resistant. This studentship builds from our recent publications that demonstrated that structural and functional overlap exists between the CpxP family of chaperones, and that they are required for Salmonella resistance to antibiotics. We believe that the CpxP chaperones present a potential new opportunity to therapeutically target Salmonella.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011216/1 30/09/2015 29/09/2023
1786329 Studentship BB/M011216/1 30/09/2016 29/09/2020 Claire Hews
 
Description Salmonella stress responses are important to the ability of the pathogen to cause infection and survive within a host. Stress responses enable bacteria, such as Salmonella, to survive in extreme conditions such as high temperature, acidic pH and are involved in resistance to antibiotics. In this study, we have identified new roles for proteins previously only thought to be involved in resistance to heat. We have shown that heat stress proteins are important for resistance to oxidative stress and for survival in a macrophage infection model. In addition, we have identified functional overlap between poorly characterised stress responsive proteins in Salmonella which furthers our knowledge into the roles of such proteins.
Exploitation Route The outcomes of this funding can be taken further in an academic setting via further funding opportunities. In addition, the outcomes will be of interest to the agricultural and healthcare sectors.
Sectors Agriculture, Food and Drink,Healthcare

 
Description Microbiology Society Travel Grant 2019
Amount £625 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 08/2019 
End 09/2019
 
Description Society Conference Grant
Amount £238 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 03/2019 
End 04/2019
 
Description Society Conference Grant
Amount £230 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 03/2017 
End 04/2017
 
Description Society Conference Grant 2018
Amount £233 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 03/2018 
End 04/2018
 
Description Collaborative review article publication 
Organisation University of Alberta
Country Canada 
Sector Academic/University 
PI Contribution Literature research, writing and editing of a review article for publication.
Collaborator Contribution Literature research, writing and editing of a review article for publication.
Impact Review article published in Frontiers in Cellular and Infection Microbiology DOI: 10.3389/fcimb.2019.00313
Start Year 2019