Prof Colin Kleanthous

Prof Colin Kleanthous

Prof Colin Kleanthous

Protein-protein interactions in the bacterial cell envelope

Bacteria envelope themselves in robust layers of membrane and cell wall that are vital to their survival. My lab investigates interactions between proteins that build and maintain this cell envelope in Gram-negative bacteria. We also investigate how protein antibiotics known as bacteriocins, which are produced naturally by bacteria in order to kill their competitors, exploit protein-protein interactions to navigate through the cell envelope. We use a variety of biochemical, structural, biophysical and cell-based approaches to address three areas:
 

  1. Protein bacteriocins – We study how these 40-80 kDa toxins assemble translocon complexes at the cell surface and how these trigger import across one or both membranes of the bacterium. Our principal target organisms also happen to be major pathogens that have seen dramatic rises in multidrug resistance, including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Serratia marcescens. Consequently, we are also evaluating protein bacteriocins as potential species-specific antibiotics.
     
  2. Outer membrane protein organisation – We recently discovered that beta-barrel outer membrane proteins cluster into large island-like structures the formation of which helps bacteria change the protein composition of the membrane. We are investigating the spatiotemporal basis for this organisation and the impact it has on the biology of the cell envelope.
     
  3. Outer membrane stabilisation – The Tol-Pal system is a multiprotein assembly that plays a prominent role in outer membrane stabilisation that has remained elusive. We are looking at how the Tol-Pal assembly works, including why it is coupled to the proton motive force and how this coupling leads to force transduction through the cell envelope.
     

For further information, see: http://www.bioch.ox.ac.uk/kleanthousresearch