Biofilms are surface-associated, socially-organized bacterial communities. Biofilm infections occur in a broad range of contexts (in the lung, and essentially any biomedical implant), and are notoriously difficult to treat with antibiotics due to biofilm-related tolerance. For example, Pseudomonas aeruginosa causes persistent and lethal infections in cystic fibrosis (CF). Progress in understanding how to circumvent recalcitrant biofilm infections would be transformational, both fundamentally and clinically.
We are reaching the limits of what can be learned using exclusively traditional methods based on genetic manipulation and subsequent observation, since biofilm development depends strongly on epigenetic and communal factors. We have recently developed a general method to analyze development of bacterial biofilm phenotypes in situ. Time-lapse microscopy movies of bacteria are translated into searchable databases. ’Search engines‘ are used to find in these movies all examples of specific events in the bacterial life cycle, such as surface attachment, cell division, or cell detachment. We can delineate the full ’geneological‘ and motility history for every individual cell in a movie. By combining this high-throughput microscopy analysis with the library of mutants available for P. aeruginosa (where 80% of the non-house keeping genes have been mutated singly and in combination), we will be able to investigate the connection between nutritional conditions, polysaccharide production, cdiGMP signaling, and surface motility in P. aeruginosa biofilm formation at the community level for the first time.
We are part of the Human Frontiers Science Program Center for Early Biofilm Development.
Here is some of our recent work.
More general references for our work on bacteria are listed below. The papers are available on our publications page.
- Zhao et al, Nature 2013
- Gibiansky et al, PNAS 2013
- Jin et al, PNAS 2011a
- Conrad et al, Biophys J 2011
- Colvin et al, PLoS Pathogens 2011
- Gibiansky et al, Science 2010
- Smalyukh et al, Phys Rev E, 2008