Birmingham BBSRC MIBTP PhD project
Principal Supervisor name, department, University:
Mark Webber, Immunity and Infection, Birmingham, m.a.webber@bham.ac.uk 0121 414 2859
Second Supervisor name, department, University:
Kumar Rajakumar, Infection, Immunity and Inflammation, Leicester
Funding status:
Competition funded Project (UK students only)
Application deadline:
31st January 2013
Project title:
To stick or twist – understanding how inhibition of multidrug efflux represses biofilm formation in
pathogenic bacteria
Project description
Bacteria attached to surfaces form biofilms which comprise cells encased within an extracellular
matrix. Biofilms are extremely antibiotic resistant and provide a clinical challenge due to their
propensity to form on artificial surfaces (prosthetics, indwelling devices etc) and the difficulty in
eradicating them. Recently Webber has demonstrated a novel functional link between bacterial
multidrug efflux systems and the ability to form a biofilm and shown using Salmonella as a model
that loss of function of any of the multidrug resistance (MDR) efflux systems of Salmonella by
genetic or chemical inactivation results in a loss of biofilm formation. Initial investigations have ruled
out a role for efflux of any biofilm promoting substance or any change in cellular adhesion or
aggregative ability in response to lack of efflux activity. Webber has demonstrated that the inability
to form a biofilm is mediated by a transcriptional repression of the curli loci – curli makes up a major
part of the Salmonella extracellular matrix. Additionally Webber has shown that key regulators of
MDR efflux systems (up-regulated in response to loss of function of efflux pumps) can recapitulate
the biofilm defect when over-expressed and this is also associated with curli repression. However
inactivation of these regulators in efflux mutants does not rescue biofilm formation. Finally it has
been shown that the link between efflux and biofilm formation appears to be conserved in diverse
bacteria with a similar effect being seen in E. coli, Pseudomonas, Klebsiella, S. aureus and
Acinetobacter.
This project aims to identify the regulatory sensors and switches which translate a loss of efflux
activity into an inability to form a biofilm – we will use both Salmonella and Acinetobacter as models
representing two divergent but major pathogens in which the supervisors have developed expertise
in working with. A combination of transcription profiling, transposon mutagenesis and specific gene
mutation and over-expression will be used to define the roles of key loci in mediating a link between
efflux function and biofilm formation. This project will allow the commonalities and species specific
differences in regulatory switches to be identified and inform development of broad spectrum antibiofilm approaches in future.
Key experimental skills involved:
Basic microbiology, molecular microbiology, various biofilm formation assays, efflux activity assays,
genomics, transcriptomics, functional genomics
Funding notes
This project is available as part of the Midlands Integrative Biosciences Training Partnership (MIBTP
between the Universities of Warwick, Birmingham and Leicester.
Please send the completed form to Holly Etchell (h.etchell@bham.ac.uk)
Birmingham BBSRC MIBTP PhD project
Students will receive a stipend of £13,590 per annum (plus £600 travel allowance in year 1, and a
MacBook Pro). More details of the scheme can be found:
http://www.birmingham.ac.uk/research/activity/mibtp/index.aspx
Reference
Baugh S., Ekanayaka A.S., Piddock L.J.V. and Webber M.A. (2012) Loss of or inhibition of all
multidrug resistance efflux pumps of Salmonella enterica serovar Typhimurium results in impaired
ability to form a biofilm. J Antimicrob Chemo Oct;67(10):2409-17
Subject areas
Biological & Medical Sciences: Biochemistry, Bioinformatics, Genetics, Microbiology, Molecular
Biology.
Please send the completed form to Holly Etchell (h.etchell@bham.ac.uk)