Biofilms have proved to be a persistent problem,primarily because of there ability to house and protect pathogenic bacteria. This problem is amplified by the fact that after maturation of a biofilm, bacteria can leave and form biofilms in neighboring tissue. Currently there are several methods to kill bacteria in biofilms and degrade the matrix that holds bioflims together, some of which are commercially available; however, a method to destroy bacteria protected by mucus at the base of biofilms has yet to be established.This base can be particularly troublesome because of the ability of biofilms to reform despite removal of the upper layers.
We would like to investigate the ability of phage to eliminate bacteria present in mucus at the base of biofilms. There are currently methods to degrade biofilms, in the form of bacteriophage and matrix degrading enzymes; however, there is no viable way to penetrate the mucus that houses the bacteria that start the biofilm. We hope to find a method to transport bacteria-killing phage past the mucus membrane to eliminate bacteria that start the biofilm. While this ability to degrade biofilms will prove useful in general, we are pressing forward in the hopes of treating patients with cystic fibrosis.
In order to do this we hope to take advantage of the innate ability of phage to destroy bacteria. It is well known that viruses have the ability to undergo two “cycles”: the lytic cycle and lysogenic cycle. In the lytic cycle, the phage uses the bacterial machinery to produce more phage until finally releasing new phage by destroying the membrane. The lysogenic cycle, on the other hand, involves phage DNA being incorporated into the host genome which can later be released.
Because viruses cannot traverse the mucus barrier, we hope to transport viral DNA using bacteria already present in biofilms. We aim to develop phage that enter the lysogenic cycle in bacteria that naturally migrate to the base mucus in biofilms. While specifics have yet to be decided on, we have found documentation suggesting the presence of certain proteins can induce integration of phage DNA. Once the bacteria, now carrying phage DNA, penetrate the mucosal barrier we will stimulate them to enter the lytic cycle. After this, the phage will presumably leave the bacteria and go on to infect surrounding bacteria.
1. Costerton, J. W., Phillip S. Stewart, and E. P. Greenberg. "Bacterial Biofilms: A Common Cause of Persistent Infections." Science 284.5418 (199): 1318-322. Http://www.sciencemag.org/content/284/5418/1318.long. Web. 06 May 2013. <http://www.sciencemag.org/content/284/5418/1318.long>.
2. Hindmarsh, Patrick, and Jonathan Leis. "Retroviral DNA Integration." Microbiology and Molecular Biology Reviews 63.4 (1999): 836-43. NCBI. Web. 06 May 2013. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC98978/>.