JOINT MATHEMATICS COLLOQUIUMUNIVERSITY OF IDAHOWASHINGTON STATE UNIVERSITY |
|---|
|
Abstract |
|---|
| Motivated by a mounting tide of drug
resistant bacteria, the search for new antibacterial agents is
embracing technologies that lie outside traditional bounds. One
promising source of compounds is the lysins encoded by bacteriophages
(viruses that infect and kill bacteria). These enzymes degrade the
bacterial cell wall from the inside, leading to rupture of the cell and
subsequent dispersal of phage progeny. Lysins have evolved to not kill
cells from the outside, thus preserving future hosts, but recent lab
work has shown that they can be engineered to kill from without.
Developing lysins that have desirable properties for therapeutic use is
complicated by the fact that the molecular basis of improvement is not
yet understood. A possible way forward is provided by directed
evolution. Here we propose lab protocols that involve the co-culturing
of two bacterial species--one producing a toxin/lysin that kills the
other, leading to selective pressure for improved function of the
toxin. We use mathematical models and simulations to explore the
feasibility of this directed evolution and offer insights into various
protocols.
|