Team:WPI-Worcester/Future-Applications
Future Applications
Going forward, there are many applications for biofilm inhibition. Since our research focuses on modified bacteria self-inhibiting by expressing AFPs themselves, a variation on phage therapy could be deployed: though phage therapy typically takes advantage of the properties of lytic phages, which cause lysis of bacterial cells (Carlton 1999), lysogenic phages, which incorporate their genome into bacterial genomes, could be used to insert AFP genes into pathogenic bacteria to inhibit their ability to form biofilms, or potentially to reverse biofilm formation. Lytic phage therapy shows promise, but lysing bacteria that contain endotoxins can have disastrous results, making biofilm inhibition a better candidate for treatment. Non-lytic phages have already been tested as therapeutic agents, with promising results (Paul et al. 2011, Matsuda et al. 2005). It would also be possible to take an approach similar to that of the authors of the original 2014 study, and coat materials such as catheters (or potentially food production machines and other items in industries in which biofilms are a common problem) with these antifreeze proteins or characteristic peptides.
One of the most interesting aspects of our results is that some AFPs were shown to increase instead of decrease biofilm production. The ability to increase or decrease biofilm production as needed could be beneficial for a variety of materials applications; for example, in 2014, Chen et al. created a biofilm-based circuit that could be induced as needed. They used an inducible system allowing the expression of curli fibrils to be controlled at the translational level, providing a model system for the induction or repression of gene expression that affects biofilm formation. Cells engineered to express AFPs could contain a similar system with slightly more complexity, in which biofilm inhibition could be achieved by the induction of an inhibiting AFP and repression of an enhancing AFP, and vice versa: biofilm formation could be achieved by the repression of the inhibiting AFP and induction of the enhancing AFP.
A simplified schematic of the proposed dual induction circuit.
Resources
Carlton, R. M. Phage therapy: past history and future prospects. (0004-069X (Print)).
Chen, Allen Y., Zhengtao Deng, Amanda N. Billings, Urartu O. S. Seker, Michelle Y Lu, Robert J. Citorik, Bijan Zakeri, and Timothy K. Lu. 2014. Synthesis and patterning of tunable multiscale materials with engineered cells. Nat Mater 13 (5):515-523.
Matsuda, T., David W. Freeman Ta Fau - Hilbert, Michael Hilbert Dw Fau - Duff, Michele Duff M Fau - Fuortes, Philip P. Fuortes M Fau - Stapleton, John M. Stapleton Pp Fau - Daly, and J. M. Daly. Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model. (0039-6060 (Print)).
Paul, V. D., Sanjeev Saravanan Sundarrajan S Fau - Rajagopalan, Sukumar Rajagopalan Ss Fau - Hariharan, Nanjundappa Hariharan S Fau - Kempashanaiah, Sriram Kempashanaiah N Fau - Padmanabhan, Bharathi Padmanabhan S Fau - Sriram, Janakiraman Sriram B Fau - Ramachandran, and J. Ramachandran. Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection. (1471-2180 (Electronic)).
