Engineered Glowing Bacteria to Design New Drug Delivery System

Bacteria that glow in synchronised bursts - a breakthrough that establishes that the cellular activity can be controlled artificially and can help in designing a new way of drug delivery has been made by American scientists.

It is expected that controlling synchrony between cells would also aid in new discoveries about sleep, learning and brain disorders like Parkinson's and Alzheimer's, which are believed to occur when the coordination between neurons is abnormal.

"It is a quantum leap in molecular clock design...It is a feat analogous to engineering all the world's traffic lights to blink in unison," New Scientist quoted Martin Fussenegger of the Swiss Federal Institute of Technology in Zurich, the author of an accompanying commentary on the research in Nature but not a part of the study, as saying.

Jeff Hasty at the University of California, San Diego, and his team took elements from a natural communication system used by bacteria and slime moulds known as quorum sensing to design engineered bacteria that glow in synchrony.

Quorum sensing allows bacteria to change their behaviour after reaching a critical density. For example, at high densities, the bacterium Vibrio fischeri, which lives on the skin of squid, starts glowing, helping to camouflage the squid, but V. fischeri which live in isolation don't light up, conserving their energy for swimming,

The bacteria can act in together because they consistently release a molecule called an autoinducer into their environment. At low bacterial densities, this has no role but at high enough densities the chemical accumulates, kicking off a response in all the bacteria.

Hasty and his team engineered a similar capability into Escherichia coli, which doesn't glow naturally. Using genetic engineering, they rewired E. coli to express three proteins in response to an autoinducer called AHL: an enzyme producing more AHL, a fluorescent protein and a chemical "off switch" that can shut down the expression of all three proteins once AHL attains a certain concentration.

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Thereafter, the engineered E. coli were grown in differently sized chambers, enabling different densities of cells to build up.

At low densities, the bacteria produced AHL, but not the other three proteins. At higher densities, AHL began to build inside the cells, generating a positive feedback loop that prompted the bacteria to produce more AHL and start making the other two proteins too. This made the bacteria glow, until enough of the "off switch" chemical was formed to shut down the system. The result of this was bacteria that glimmered, but each in its own rhythm.

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However, once the colony reached an even higher, critical density, enough AHL accumulated outside the cells forming a pool from which all the bacteria took their cue. At this point, the bacterial glowing became synchronised, producing light waves that spread across the bacterial colony.

Modifying the temperature, chemical composition or other conditions within the chamber brought about a change in the frequency and amplitude of the waves.

One use of the technique might be in implants made of engineered cells that would deliver pulses of insulin in response to changes in levels of blood sugar.

Source-ANI
TRI