By tagging a cell's proteins with fluorescent beacons, Cornell researchers have found out how E. coli bacteria defend themselves against antibiotics and other poisons. Probably not good news for the bacteria.
When undesirable molecules show up, the bacterial cell opens a tunnel though its cell wall and "effluxes," or pumps out, the intruders.
In the periplasm -- the space between the inner and outer membranes of a bacteria's cell wall -- defensive proteins that detect a poison assemble like barrel staves to form a tunnel between pumps in the cell's inner and outer membranes to eject the intruders. Artist's conception by Ace George Santiago.
Credit: Ace George Santiago, Cornell University
"Dynamic assembly of these tunnels has long been hypothesized," said Peng Chen, professor of chemistry and chemical biology. "Now we see them."
The findings could lead to ways to combat antibiotic-resistant bacteria with a "cocktail" of drugs, he suggests: "One is to inhibit the assembly of the tunnel, the next is to kill the bacteria."
To study bacteria's defensive process, Chen and colleagues at Cornell selected a strain of E. coli known to pump out copper atoms that would otherwise poison the bacteria. The researchers genetically engineered it, adding to the DNA that codes for a defensive protein an additional DNA sequence that codes for a fluorescent molecule.
Under a powerful microscope, they exposed a bacterial cell to an environment containing copper atoms and periodically zapped the cell with an infrared laser to induce fluorescence. Following the blinking lights, they had a "movie" showing where the tagged protein traveled in the cell. They further genetically engineered the various proteins to turn their metal-binding capability on and off, and observed the effects.
Their research was reported in the Early Online edition of the Proceedings of the National Academy of Sciences the week of June 12. The Cornell researchers also collaborated with scientists at the University of Houston, the University of Arizona and the University of California, Los Angeles.
The key protein, known as CusB, resides in the periplasm, the space between the inner and outer membranes that make up the bacteria's cell wall. When CusB binds to an intruder - in this experiment, a copper atom - that has passed through the porous outer membrane, it changes its shape so that it will attach itself between two related proteins in the inner and outer membranes to form a complex known as CusCBA that acts as a tunnel through the cell wall. The inner protein has a mechanism to grab the intruder and push it through.
The tunnel locks the inner and outer membranes together, making the periplasm less flexible and interfering with its normal functions. The ability to assemble the tunnel only when needed, rather than having it permanently in place, gives the cell an advantage, the researchers point out.
This mechanism for defending against toxic metals may also explain how bacteria develop resistance to antibiotics, by mutating their defensive proteins to recognize them. Similar mechanisms may be found in other species of bacteria, the researchers suggested.
The work was supported by the Army Research Office and the National Institutes of Health.
Daryl Lovell | EurekAlert!
New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa
New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal
A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter
A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.
Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...
The technology could revolutionize how information travels through data centers and artificial intelligence networks
Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...
Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.
Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...
Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna
A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...
17.04.2019 | Event News
15.04.2019 | Event News
09.04.2019 | Event News
18.04.2019 | Life Sciences
18.04.2019 | Physics and Astronomy
18.04.2019 | Life Sciences