Unit 4. Bacteria

Scriprt 7. Synthetic biology

Set a thief ...

Genetically engineered bacteria can be used to attack other bacterial species.

Biofilms are a problem in medicine. When bacteria gang up to form the continuous sheets that bear this name they are far harder to kill with antibiotics than when they just float around as individual cells. Biofilms on devices such as implants are thus difficult to shift, and those growing on the surfaces of human organs are frequently lethal. But Matthew Chang, a biochemical engineer at Nanyang Technological University in Singapore, has worked out a new way to attack them. His weapon is a different type of bacterium, which he has genetically engineered into a finely honed anti-biofilm missile.

The starting point for this new piece of biotechnology is a common gut bacterium called Escherichia coli. Though this species is best known to the wider world for causing food poisoning, most strains of it are benign, and it is one of the work-horses of genetics.

The story began in 2011 when Dr. Chang worked out how to program E. coli to release destructive antimicrobial peptides when they came into contact with another bacterium, Pseudomonas aeruginosa. This species, which is common in hospitals, likes to form biofilms and is a frequent cause of sepsis.

To deal with this film-forming propensity, Dr Chang did a second bit of genetic tinkering. He armed his modified E. coli with an enzyme called DNase I. Curiously, a lot of the chemical links holding individual P. aeruginosa bacteria together in a biofilm are made of DNA, a molecule more familiar as the material of genes. DNase 1 attacks DNA, and thus acts to break the film up.

That worked too, but it was still not enough to create a useful medical agent because the modified E. coli did not seek out their targets. So, as he has just reported in Synthetic Biology, Dr Chang has now done a third piece of engineering by changing his bugs' food-detection system to react to the signalling molecules that P. aeruginosa release when they are seeking to link up with their neighbours.

Laboratory tests suggest these triply armed E. coli kill P. aeruginosa biofilms six times as effectively as the version armed only with antimicrobial peptides and DNase I. This is not yet a deployable medicine, but it is a novel and intriguing approach. And it is one that might easily be used against other biofilm-forming species, by changing which signalling molecules the engineered E. coli are sensitive to. (From The Economist. October 12, 2013)

Script 8. Bioengineering

Panda poop power

Microbes in pandas’ guts can help in biofuel production.

Giant pandas are well known for being rather different from other bears. Having a diet composed almost entirely of bamboo is one of the things that sets them apart. It is also what attracted the interest of Ashli Brown of Mississippi State University, in a search for more efficient ways to make biofuel.

Most of the nutrients found in bamboo are locked away in tough substances known as cellulose and lignin. Liberating those nutrients is an energy-intensive process that involves high temperatures and extreme pressures when carried out in a laboratory or by an industrial process. Indeed, it is the cost of doing so that makes producing biofuel out of cellulose and lignin-rich materials, like discarded corn (maize) cobs and husks, less financially viable than generating biofuel directly from more readily digestible corn kernels. The kernels, however, can be used to feed people whereas the cobs and husks cannot. So a process that is able effciently to turn what is a waste product into fuel could have great potential.

Given their diet, Dr Brown knew that giant pandas had to have legions of microbes in their gut that were strong enough to break cellulose and lignin down. If it was possible to identify those microbes and find the enzymes within them they might be used to improve biofuel production. So, Dr Brown and her colleagues got to work analysing piles of panda faeces for the presence of RNA strands belonging to the microbes.

The team then searched through microbial databases to identify the genre that these microbes belonged to and determine which known species they were most closely related to. This identification process allowed Dr Brown to run a comparative analysis that teased out minor differences between the microbes to reveal which ones carried the traits that made them particularly adept at breaking down the bamboo material.

This produced 17 microbes with the ability to digest cellulose and six that looked like good candidates for digesting lignin. The microbes were then tested in the laboratory. They were found to be capable of breaking down 65.4% of the tough materials they were given and transforming much of them into the sorts of energy-rich sugars that are readily fermented into bioethanol or biodiesel, Dr Brown told a national meeting of the American Chemical Society in Indiana this week.

Considering that most cellulose- and lignin-based materials end up as compost, or worse, in landfills, the ability to convert such a large percentage of them into potential biofuel products is encouraging. Dr Brown, though, is quick to point out that optimising the performance of the enzymes employed by the microbes so that they can be used commercially is going to be a long and hard job. But thanks to the giant panda being saved from extinction, it is one that could be well worth the effort. (From The Economist, September 14, 2013)