P. Lynne Howell Professor

Ph.D., London, U.K., 1986
Hospital for Sick Children, Research Institute, Room 3507A
416-813-5378
howell@sickkids.ca

Macromolecular Complexes Involved in Bacterial Biofilm Formation


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Research Synopsis
 


Model of Pseudomonas aeruginosa alginate secretion complex.

A biofilm is a surface attached community of bacterial cells encased in a self-produced polymeric matrix. Formation of a biofilm is a multi-step process that
involves:

1. attachment of planktonic bacteria to a surface via organelles such as their type IV pili;
2. aggregation and formation of a microcolony; the production of quorum sensing molecules; and
3. the secretion of exopolysaccharides, which form the bulk of the matrix.

Biofilms grow on any moist biotic or abiotic surface, and provide a number of environmental advantages such as protecting the bacteria from the host immune response, and conferring tolerance to antibiotics and detergents. Once established biofilms are extremely difficult to eradiate, and hence are responsible for a wide-range of medical problems, including device-related infections, lung infections in cystic fibrosis patients, as well as middle ear, cochlear implant and burn related infections.

In the lab, we use a combination of microbiological, biochemical, as well as X-ray crystallographic, nuclear magnetic resonance (NMR) and other biophysical techniques to determine the three-dimensional structure and function of the macromolecular complexes involved in two steps in the biofilm life cycle.

We are interested in understanding at the molecular level the processes
involved in:

1.        The assembly of Pseudomonas aeruginosa type IV pili

2.        The biosynthesis and export of the exopolysaccharides: alginate and the pel polysaccharide from P. aeruginosa and E. coli polyß-1,6,N-Acetyl-D-glucosamine.

Our long term goal is to identify potential targets for the development of
novel antimicrobials.

 


Selected Publications
Click here for a publications list hosted by the Hospital for Sick Children.    

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