Talking to bacteria

PHILIP BALL

Altered bacteria blink on and off like lightbulbs when doused with a chemical signal. © Science Photo Library

Scientists have genetically engineered bacteria to 'talk' to each other in a new language¹. The achievement brings us one step closer to turning cells into tiny robots that we can control by flooding them with chemicals.

Bacteria already communicate with each other by sending out chemical signals. A cell might release a certain chemical in response to stress, for example, letting other cells nearby know they should prepare for some unpleasant environmental conditions. When the chemicals reach a high enough concentration, they switch on genes in neighbouring cells that change their behaviour.

But cells typically have a limited number of stimuli that provoke these chemical warnings, and a limited number of chemicals that they can use to communicate. James Liao and co-workers at the University of California, Los Angeles, wondered if they could get bacteria to talk using a different chemical.

They started by stitching a 'module' of control genes into the genome of Escherichia coli bacteria — these genes can switch on or off other genes naturally present in the bacteria. This technique has been used before. For example, four years ago researchers at Princeton University in New Jersey added a gene module to E. coli cells that made them blink on and off like light bulbs. The genes did this by prompting the cells to make a light-emitting protein called GFP in regular spurts.²

Liao and colleagues went a step further, modifying E. coli cells to produce GFP only when triggered by a chemical called acetate. Acetate is a normal by-product of the metabolism of E. coli — the cells exude it constantly, rather like sweating. So the bacteria in Liao's lab constantly told each other to light up.

You could use this approach as a Trojan horse idea to combat disease Jeff Hasty University of California

The team managed to control the conversation by adjusting the acidity of the cell medium. In non-acidic conditions, it takes more acetate to trigger a cell, so there needs to be a lot of cells secreting acetate to start the conversation. In acidic conditions, just a few cells are enough to start a chat.

Trojan horse

Liao's team persuaded the cells to make GFP simply as a convenient way to show that the acetate trigger was working. But in principle, they could use the acetate signal to trigger cells to do something more practical, such as making hydrogen or producing poisons to kill off diseased cells.

"You could use this approach as a Trojan horse idea to combat disease," says Jeff Hasty, who works on gene modules at the University of California, San Diego. Modified cells of pathogenic bacteria could be introduced into a natural colony of the same cells, he says. Then, at a given chemical signal, the modified cells could be told to produce compounds that would kill off the bacteria.

Liao and colleagues think they can use the same technique to talk to other species of bacteria too. Eventually, they hope to create dialogue in diverse communities of cells that would ordinarily just ignore each other.

1. Bulter, T. et al. Design of artificial cell-cell communication using gene and metabolic networks. Proceedings of the National Academy of Sciences USA, advance online publication, doi:10.1073/pnas.0306484101 (2004).
2. Elowitz, M.B.. & Leibler, S.. A synthetic oscillatory network of transcriptional regulators. Nature, 403, 335 - 338, advance online publication, doi:10.1073/pnas.0306484101 (2000).

© Nature News Service / Macmillan Magazines Ltd 2004