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Summers Group

Microbial Genetics and Cell Signalling

Keywords

Escherichia coli, bacterial plasmids, cell signalling, control of the bacterial cell cycle, indole, stress responses, bacterial cell factory

Research interests

Research in the Summers laboratory focused originally on plasmids of the bacterium E. coli and the mechanisms by which they ensure their stable inheritance. An unexpected discovery emerging from this work was that the multicopy plasmid ColE1, when damaged by dimerization, prevents the division of its bacterial host. This is achieved via a cell division checkpoint mediated by a 70 nt RNA, Rcd. The transcript binds the enzyme tryptophanase, and stimulates indole production.

Working in collaboration with Dr Ulrich Keyser's group at the Cavendish Laboratory, we demonstrated that indole blocks cell division by acting as a proton ionophore (a molecule that conducts ions through a lipid membrane). This represents an entirely novel mechanism of cell cycle control. At the same time we found that indole inhibits the type II topoisomerase DNA gyrase.

As a result of these discoveries, the focus of the Group’s research has shifted towards bacterial signalling, and to indole signalling in particular. We have demonstrated the existence of two modes of indole signalling. Persistent signalling involves low indole concentrations for an extended period (several hours) while pulse signalling requires a high concentration for a short period (just a few minutes).

Our current priority is to investigate the roles of the two indole signalling modes in the field of bacterial stress responses. We have already explored responses to stress triggered by heat and resource limitation and have now turned our attention to antibiotic-generated stress. We are looking closely at the role of indole in bacterial antibiotic resistance and, in particular, the mechanism by which it generates persister cells that enter a dormant state to survive killing by the antibiotic.

Applied research

The laboratory has been actively involved in the commercialisation of discoveries arising from its basic research program. One major achievement has been the development of the Quiescent Cell Expression System (Q-Cells), a novel bacterial cell factory for the expression of metabolites in non-growing E. coli.

A second area of interest is the application of research on indole signalling to the development of anti-persister drugs. We are currently exploring the production of enhanced versions of a number of DNA gyrase inhibitors.

Key publications

  1. Gaimster, H. and Summers, D. (2015) Regulation of Indole Signalling during the Transition of E. coli from Exponential to Stationary Phase. PLoS One 10(9): e0136691
  2. Gaimster, H. and Summers, D. (2015) Plasmids in the driving seat: The regulatory RNA Rcd gives plasmid ColE1 control over division and growth of its E. coli host. Plasmid 78: 59-64
  3. Gaimster, H., Cama, J., Hernández-Ainsa, S., Keyser, U.F. and Summers D.K. The indole pulse: a new perspective on indole signalling in Escherichia coli. PLoS One. 2014 Apr 2; 9(4):e93168
  4. Chimerel, C., Field, C.M., Pinero-Fernandez, S., Keyser, U.F., and Summers, D.K. (2012). Indole prevents Escherichia coli cell division by modulating membrane potential. Biochimica et Biophysica Acta 1818, 1590-1594
  5. Field, C.M., and Summers, D.K. (2011). Multicopy plasmid stability: Revisiting the dimer catastrophe. J Theor Biol 291, 119-127
  6. Pinero-Fernandez, S., Chimerel, C., Keyser, U.F., and Summers, D.K. (2011). Indole transport across Escherichia coli membranes. Journal of Bacteriology 193: 1793-1798
  7. Summers, D. K. and Chant, E. (2010). Chemical induction in quiescence in bacteria. USPTO. United States Patent number 7,790,435
  8. Blaby, I.K. and Summers, D.K. (2009) The role of FIS in the Rcd checkpoint and stable maintenance of plasmid ColE1. Microbiology 155: 2676-2682

>> Full list of publications on PubMed

 

Page updated 19 October 2017

Contact details

Group leader : Dr David Summers

Address:
Department of Genetics,
University of Cambridge,
Downing Street,
Cambridge CB2 3EH,
United Kingdom

Email: d.summers@gen.cam.ac.uk

Tel.: +44 (0)1223 333991 [office]
+44 (0)1223 333985 [lab]

Group members