Issue Date: January 16, 2012
Bacteria Array Detects Arsenic
A new device harnesses the synchronized oscillations of millions of bacteria to continuously detect the metal arsenic (Nature, DOI: 10.1038/nature10722). One possible use for the device is to detect arsenic in drinking water.
Jeff Hasty and coworkers at the University of California, San Diego, made their arsenic sensor using an array of engineered Escherichia coli that produce oscillating genetic clocks and synchronize the oscillations within and between colonies. Each bacterial colony is located in a different well of a microfluidic device.
Hasty engineered the bacteria with two communication systems that operate on different length scales but are part of the same genetic circuit. Over short distances, the bacteria within each colony synchronize their clocks by communicating with one another using acyl-homoserine lactone, a small molecule used in the bacterial communication system known as quorum sensing. Over longer distances, separate colonies synchronize their oscillations using redox signaling with hydrogen peroxide gas.
The two levels of communication allow the array to be larger than would be possible with quorum sensing alone. Quorum sensing is limited by the diffusion rate of the acyl-homoserine lactone and breaks down on longer length scales. “To get to the centimeter length scale, you need a very fast communication scheme. That’s what this redox signaling allows you to achieve,” Hasty says.
To create these two communication systems, Hasty’s team programmed bacteria with genetic circuitry containing machinery for quorum sensing, a hydrogen peroxide-producing enzyme, and a fluorescent protein. The fluorescent protein allows the oscillations to be detected optically. The same promoter drives transcription of all the genes in the circuit, and both acyl-homoserine lactone and hydrogen peroxide provide positive feedback that synchronizes the oscillations.
The genetic circuit also includes an extra copy of the lactone-producing machinery under the control of another promoter, which binds arsenic. In the absence of arsenic, the circuit functions normally. But when the promoter binds arsenic, it turns on additional gene transcription that modulates the period and amplitude of the oscillations. The period is proportional to the amount of arsenic.
Thousands of colonies oscillating in sync generate a strong enough fluorescence signal to be detected with inexpensive excitation sources and optics, Hasty says. The device is able to detect arsenic concentrations as low as 0.25 μM, which is below the World Health Organization’s recommended level of approximately 0.5 μM for developing countries but above the U.S. standard of 10 ppb, or about 0.13 μM.
The sensor is a continuous monitoring system. “Once you set it up, it behaves like a chemostat and can monitor a sample continuously over long periods of time,” Hasty says.
But the sensors are not without their challenges. They are slow. Each oscillation takes about an hour, Hasty says, and it takes about five cycles to lock in the period. He thinks they will be able to cut the period to about 10 minutes by further engineering the bacteria.
An arsenic sensor is just one of many types of sensors that could be made this way, Hasty says. But for the near term, he says, “you want to focus on substances that bacteria naturally sense,” such as heavy metals and pathogens.
The work “represents an important advance for synthetic biology, one that positions the field nicely for a range of biosensing capabilities,” says James J. Collins of Boston University, an expert in synthetic biology.
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