Saturday, 20 August 2011

Bug-Bombing Biofilms

This weeks's Science Now has a really cool example of the awesome power of genetics and genetic engineering. Published in Molecular Systems Biology, a paper by Nazanin Saeidi et al. describes the construction of a bacterial bomb designed to take out Pseudomonas aeruginosa, which is a nasty biofilm-forming human pathogen.

Traditionally, we think about bacteria a single-celled organisms but this is often not really the case. In many situations, populations of bacteria form multicellular masses called biofilms. These can be a big problem, particularly for human disease, because the biofilm structure can make the bugs resistant to regular antibiotic attack.

Bring in the Special Forces. Saeidi et al. took another bacterium - workhorse of the molecular biology lab, Escherichia coli - and pimped it out to be a Pseudomonas aeruginosa killing machine, using many of the own pathogen's weapons against it. Essentially, the system was comprised of three parts:

1. The E. coli were engineered to recognise the "quorum sensing" signals that the Pseudomonas naturally produce to communicate during biofilm formation.

2. The quorum sensing receptor was genetically wired up to a gene that produced a toxin, pyocin, that had been modified to kill Pseudomonas. (In fact, they modified the very toxin that Pseudomonas uses to kill other bacteria during biofilm formation.)

3. The sensor was also wired up to a self-destruct mechanism, switching on expression of a lysis protein that, once enough had accumulated, would cause the cell to burst.

The net result is an E. coli that can sense when it is near Pseudomonas biofilms and, once the density is high enough, will start producing the pyocin toxin and the self-destruct lysis protein. After a period of accumulation, the cell bursts and all the surrounding Pseudomonas are exposed to the toxin, hopefully killing them.

The paper was just proof of principle, really. They were able to kill 90-99% of Pseudomonas aeruginosa with their new bug-bomb but there are still a lot of hurdles to overcome before this could be considered as a treatment for Cystic Fibrosis and other biofilm-related diseases. For one thing, it is not clear how harmful the E. coli, itself a human pathogen, or its toxic cargo would be to the patient or the other "friendly" bacteria in their bodies.

Despite this, though, I still think it is cool. Just being able to engineer something like this that works is a demonstration of how awesome molecular biology and genetics is in the 21st Century. Even if human diseases cannot be targeted directly with such techniques, biofilms also cause problems outside the body, such as in water pipes or on surgical instruments, and having another potential weapon in the arsenal to fight them is always welcome.

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