Bacteria use small circuits of genes to manage routine tasks like copying their DNA or neutralizing a toxin. Now researchers have rewired one such gene circuit to control the size of bacterial populations. The results offer a new strategy for engineering microbes, and they promise a potential safety switch that would make bugs die once they've done their job.
In the 1970s, genetic engineers began inserting genes into microbes and enlisting them to make drugs or insecticides. Recently biologists have begun reprogramming cells to carry out much more complex jobs, such as sensing bioweapons or cleaning up pollutants. But getting a swarm of microbes to work together can be as hard as herding cats; cells in a given population tend to work at cross purposes.
To better coordinate bacteria, bioengineers Lingchong You and Frances Arnold of the California Institute of Technology and colleagues rewired a natural cell-signaling pathway from Vibrio fisheri, bacteria in the light organ of deep-sea squid. The pathway normally enables the bacteria to glow when their population reaches a certain size. In nature, quorum-sensing genes make each bacterium pump out a chemical called an autoinducer, which accumulates as the population grows. Individual bacteria switch on their bioluminescence genes when they detect enough of the autoinducer in their environment.
Stealing this trick, the team transplanted the quorum-sensing genes into Escherichia coli and rigged them to turn on a cell-suicide gene. Bacteria began to die off as their numbers reached a certain level, they report online 4 April in Nature. The researchers could also adjust the population size that tripped the fatal switch. A more alkaline growth medium, for example, made the autoinducer less stable, slowing activation of the cell-suicide gene and increasing the population.
"This is a cool study that shows you can harness the power of natural circuits that have evolved over a very long time," says bioengineer Jim Collins of Boston University. With modifications, he notes, such a circuit could enable bacteria to kill themselves after they've completed their task, or after a certain number of generations--thus creating a safety device that would keep engineered cells from escaping into the environment.