Investigating the transcriptional control of antibiotic resistance mechanisms

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

The bacterial species Streptomyces has given rise to 70% of commercially used antibiotics. As well as being producers of antibiotics they also contain resistance mechanisms. Some of these are encoded within plasmids that can be transmitted to other bacteria leading to widespread antimicrobial resistance. One such example is the Streptomyces coelicolor A3(2) plasmid which contains the biosynthetic genes for both production and resistance of the antibiotic methylenomycin. While certain genes within the cluster has been studied in varying detail the activator (MmyB) and repressor (MmyJ) of the methylenomycin resistance gene mmr is still lacking in characterisation. The aim of this PhD is to characterise MmyJ and MmyB structurally and functionally as well as any additional proteins within the gene cluster contributing to the control of methylenomycin resistance. Analysis of these transcriptional regulators can contribute to antibiotic resistance mechanisms and aid the development of an alternative inducible system.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 31/03/2024
1897466 Studentship BB/M01116X/1 02/10/2017 02/01/2022 Rohini Ajaykumar
 
Description *Still ongoing work*

This work is on antibiotic resistance in bacteria important in the emergence of multi-drug resistance bacteria. Discovery is still ongoing but there have been new insights into the mechanism of the workings of the resistance of the antibiotic methylenomycin in Streptomyces bacteria. These results so far show that there is a blocking of the molecule that exports methylenomycin from the bacterial cell. The molecule that blocks this exporting mechanism is unblocked in the presence of methylenomycin. The specifics of this is being researched. This information would be valuable in manipulating this mechanism for biotechnological needs as to contribute vital knowledge into antibiotic resistance.
Exploitation Route The outcomes would provide valuable insights into the workings of antibiotic resistance. It could be used in biotechnology as an alternative mechanism to creating inducible expression of certain genes which at the moment, with the most popular method relies on expensive and hard to produce chemicals. Furthermore, this could be a starting point to finding new unknown mechanisms into resistance by bacteria of other antibiotics.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description Soapbox Science Outreach 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Event in which general public roughly 50 people coming and going, were engaged in science through a short talk and different activities, encouraging more into STEM.
Year(s) Of Engagement Activity 2019