About the Project
Understanding the multiple antibiotic resistance gene regulatory system of enteric pathogens
In human pathogens, including Escherichia coli and Salmonella species, a small group of AraC-XylS family transcription factors drive resistance to antibiotics by altering gene expression. The primary example is the multiple antibiotic resistance activator, MarA, protein of E. coli (1,2). Antibiotic resistant bacteria can carry genetic changes meaning MarA is produced all the time and at high levels (2). Upon expression, MarA alters gene expression globally, by binding DNA sites called marboxes, and this drives antibiotic resistance (1,2). Whilst some aspects of the response are understood, such as up-regulation of efflux pump expression, most MarA regulated genes are unknown or have no obvious connection to drug resistance (2).
We have developed an approach to accurately identify MarA regulated genes (2). Furthermore, by mutating marboxes at different chromosomal sites, we have discovered strong synergistic interactions, between regulated genes, that individually appear inconsequential (3). This project will build on these findings to answer two major questions: which genes are controlled by MarA and how do synergistic interactions between them drive antibiotic resistance? You can expect to learn a wide range of molecular biology techniques, both laboratory based and computational. The lab approaches will include whole genome and focused molecular microbiological tools.
Funding Notes
Funded by the MIBTP/BBSRC training programme (all students).
You can apply by following this link Understanding multiple antibiotic resistance mechanisms in pathogenic bacteria and registerng for our application system. The link covers two related projects in our lab, you do not need to further specify the particular project you're interested in.
The link View Website provides further important details of the MIBTP programme that you should read when applying.
References
- Blair, J. M. A. et al. Nature Reviews Microbiology 13, 42–51 (2015)
- Sharma, P. et al. Nat. Commun. 8, [contact details available in the full listing])
- Trigg, A. et al. PLoS Genet. 21: e[contact details available in the full listing])
