Quest for designer bacteria uncovers a 'Spy'

Feb 14, 2011
A cradle-shaped molecular assistant called Spy aids in protein refolding and protects unstable proteins from being cut up or sticking to other proteins. Credit: Shu Quan

Scientists have discovered a molecular assistant called Spy that helps bacteria excel at producing proteins for medical and industrial purposes.

Bacteria are widely used to manufacture proteins used in medicine and industry, but the bugs often bungle the job. Many proteins fall apart and get cut up inside the before they can be harvested. Others collapse into useless tangles instead of folding properly, as they must in order to function normally.

A research team led by James Bardwell, who is a professor of molecular, cellular and and of biological chemistry, as well as a Howard Hughes Medical Institute investigator, at the University of Michigan, developed a way to coerce bacteria into making large quantities of stable, functional proteins. Then, in exploring why these designer bacteria were so successful, the scientists discovered the molecular helper, Spy.

The research is scheduled for online publication Feb.13 in the journal Nature Structural & Molecular Biology.

In the first phase of the research, the team designed biosensors that directly link protein stability to the antibiotic resistance of bacteria. When a poorly folded, unstable protein is inserted into the middle of the biosensor in a bacterium, it disrupts the bug's resistance to antibiotics. When the protein is stabilized, resistance is restored.

The researchers inserted a particularly unstable protein into Escherichia coli (E. coli), which forced the bacteria to either adapt by improving protein stability or die when exposed to antibiotics. Through a "directed evolution" experiment, in which the scientists selected colonies with increasing antibiotic resistance---and increasing protein stability—the team generated designer bacteria that produced up to 700 times more of the previously unstable protein.

"It is exciting to realize that if even bacteria are asked in the right way, they can come up with good solutions to hard problems," said postdoctoral fellow Shu Quan, who spearheaded the work.

In looking to see why the designer bacteria were so much better at producing proteins, the scientists found that the efficient microbes were making much more of a small protein called Spy. Further study showed that the cradle-shaped Spy aids in refolding and protects unstable proteins from being cut up or sticking to other proteins.

"Our work may usher in an era of designer bacteria that have had their folding environment customized so that they can now efficiently fold normally unstable proteins," Bardwell said.

Explore further: Life's extremists may be an untapped source of antibacterial drugs

More information: Nature Molecular and Structural Biology: www.cell.com/molecular-cell/home

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jscroft
1 / 5 (2) Feb 14, 2011
Well, on the one hand this is genius. On the other hand, it's worth pointing out that, by using antibiotic resistance as their cost function, the researchers are giving these bacteria a crash course in virulence.

One hopes their containment facility is state-of-the-art.
pauljpease
5 / 5 (2) Feb 14, 2011
Well, on the one hand this is genius. On the other hand, it's worth pointing out that, by using antibiotic resistance as their cost function, the researchers are giving these bacteria a crash course in virulence.

One hopes their containment facility is state-of-the-art.


Actually, the antibiotic they are using is of limited medical use. This kind of thing is done THOUSANDS of times every day around the world. There is more risk of creating a super-bug by you not taking your full ten day course of medication than from these basic and routine experiments. Plus, if you read the article carefully, the scientists actually disrupted the bacteria's resistance, and then selected for colonies that improved their resistance, they aren't making super resistant strains.

Just an annoyance of mine, when people have no idea what they're talking about but decide to add ignorance and fear to the discussion, it's just not a winning situation for science.
kaasinees
2.5 / 5 (2) Feb 14, 2011
Any genetic alternations to bacteria to make them better at certain tasks will most certainly destroy their resistance it is not intentionally it is naturally. This also means that if they do get loose they will be easily destroyed by natural selection/competitors since they are not evolved/adapted to that environment.

Also bacteria that evolve to be resistand to antibiotics become vurnerable to super-antibiotics and also the other way around. Bacteria simply have no chance against human beings in these days.
Parsec
not rated yet Feb 14, 2011
Any genetic alternations to bacteria to make them better at certain tasks will most certainly destroy their resistance it is not intentionally it is naturally. This also means that if they do get loose they will be easily destroyed by natural selection/competitors since they are not evolved/adapted to that environment.

Also bacteria that evolve to be resistand to antibiotics become vurnerable to super-antibiotics and also the other way around. Bacteria simply have no chance against human beings in these days.


I agree with the first part completely.

However as to the second part, you have a very outdated view of the state of antibiotic research and the challenges of antibiotic resistance. Super-bugs are evolving faster than antibiotics are being developed.
kaasinees
1 / 5 (1) Feb 14, 2011
However as to the second part, you have a very outdated view of the state of antibiotic research and the challenges of antibiotic resistance. Super-bugs are evolving faster than antibiotics are being developed.


Yes you are correct on that one, i was being a bit premature on that part. MRSA is a perftect example i think, but the problem on that is our own immune system, not the antibiotics. Recent development now know what MRSA is really doing.

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