Microbial Genetics and Cell Signalling
Escherichia coli, bacterial plasmids, cell signalling, control of the bacterial cell cycle, indole, stress responses, bacterial cell factory
Research in the Summers laboratory focussed originally on plasmids of E. coli and the mechanisms by which they ensure their stable inheritance. We demonstrated why plasmid dimer formation has a detrimental effect on plasmid maintenance and identified the mechanisms by which the plasmid counters this threat.
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, that binds the enzyme tryptophanase, and stimulates indole production. Working in collaboration with Dr Ulrich Keyser at the Cavendish Laboratory, we demonstrated that indole blocks cell division by acting as a natural ionophore (a molecule that conducts ions through a lipid membrane in the absence of a protein pore). This represented an entirelynovel mechanism of cell cycle control. At the same time we found that indole inhibits plasmid replication by acting directly to inhibit DNA gyrase.
The elucidation of the mechanism of the Rcd checkpoint moved the focus of the group’s research towards bacterial signalling, and onto indole signalling in particular. Recently we have discovered an important role for indole signalling as E. coli makes the transition from exponential growth to stationary phase. The change of growth phase is accompanied by a brief (10-15 min) pulse of indole that transiently reaches >50 mM in the cells producing it.
Our current priority is to gain a better understanding of the mechanism of pulse signalling and to explore its role in bacterial responses to stress, including antibiotic action.
The laboratory has been actively involved in the commercialization 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. Companies or individuals interested in using the Q-Cell system commercially or in their research should contact David Summers.
- 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
- Field, C.M., and Summers, D.K. (2011). Multicopy plasmid stability: Revisiting the dimer catastrophe. J Theor Biol 291, 119-127
- 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
- Summers, D. K. and Chant, E. (2010). Chemical induction in quiescence in bacteria. USPTO. United States Patent number 7,790,435
- 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
- Chant, E.L., and Summers, D.K. (2007) Indole signalling contributes to the stable maintenance of Escherichia coli multicopy plasmids. Molecular Microbiology 63: 35-43
- Balding, C., Blaby, I. and Summers, D. (2006) A mutational analysis of the ColE1-encoded cell cycle regulator Rcd confirms its role in plasmid stability. Plasmid 56: 68-73
- Mukherjee, K. J., Rowe, D.C.D., Watkins, N.A. and Summers D.K. (2004) Studies on Single Chain Antibody Expression in Quiescent Escherichia coli. Applied and Environmental Microbiology 70: 3005-3012