[DIYbio] Suicide bacteria engineered to kill other bacteria (E.coli and P.aeruginosa)

Suicide bacteria engineered to kill other bacteria
http://www.cbsnews.com/stories/2011/08/16/scitech/main20093071.shtml


In a lab in Singapore, scientists are designing and breeding suicide
bombers. If their efforts pan out, they will be applauded rather than
jailed, for their targets are neither humans nor buildings. They're
bacteria.

Nazanin Saeidi and Choon Kit Wong have found a new way of killing
Pseudomonas aeruginosa, an opportunistic species that thrives wherever
humans are weak. It commonly infects hospital patients whose immune
systems have taken a hit. It targets any tissue it can get a foothold
on - lungs, bladders, guts - and it often causes fatal infections. To
seek and destroy this threat, Saiedi and Wong have used the common lab
bacterium Escherichia coli as a sacrificial pawn.

Their E.coli recruits produce a protein called LasR, which recognises
molecules that P.aeruginosa cells use to communicate with one another.
When LasR detects to these chemical signals, it switches on two genes.
The first one arms the bomb. It produces pyocin, a toxin that kills
P.aeruginosa by drilling through its outer wall and causing its
innards to leak out. The second gene detonates the bomb. It produces a
protein that causes the E.coli to burst apart, killing itself but also
releasing a flood of deadly pyocin upon nearby P.aeruginosa.

http://blogs.discovermagazine.com/notrocketscience/files/2011/08/E.coli-suicide-bombers.jpg

The beauty of this solution is that it uses P.aeurginosa's own weapons
against it. Pyocins are actually a P.aeruginosa innovation. When times
are tough, these opportunists use pyocins to kill off competing
strains. Saeidi and Wong focused on one of these weapons - a pyocin
known as S5. It comes in two parts: one does the killing; the other
makes the host cell immune to its own weapons. By arming their bombers
with pyocin S5, Saeidi and Wong found that they could kill many
P.aeruginosa strains that cause problems for hospital patients.

In preliminary lab tests, the E.coli bombers proved to be remarkably
effective against P.aeruginosa. When the two species were mixed
together, the bombers took out around 99% of their targets. They even
killed around 90% of cells in slimy communities of P.aeruginosa called
biofilms. Biofilms are like bacterial cities and they are notoriously
hard to destroy. The E.coli bombers levelled them.

Of course, Saeidi and Wong's method is a long way from actual clinical
use. They haven't even tested their suicide bomber bacteria in a live
animal yet, much less in human patients. This is merely a proof of
principle. Even so, it's hard not to get excited about scientists
exploring ingenious new ways of tackling infectious bacteria. We are,
after all, losing the war against such microbes.

The development of new anti-bacterial drugs has ground to a halt. The
vast majority of antibiotic classes were created between the 1940s and
1960s, with only two new ones entering the market in the last decade.
Meanwhile, bacteria have been evolving resistance to current arsenal,
and people have already documented strains that resist virtually all
of our known drugs.

P.aeruginosa is particularly hard to treat because it's already
naturally resistant to a large variety of antibiotics. It has a number
of molecular pumps that evict any drug that gets inside it. Doctors
often try to treat it by hitting it with a number of different drugs,
but it can shift to a dormant and tolerant state, where it survives by
keeping its head down. Meanwhile, the drug onslaught harms helpful
bacteria that normally colonise our bodies.

As an alternative, some scientists have tried using viruses called
phages, which target and kill bacteria. They've had some success in
mice but Saeidi and Wong think that this approach has problems. It can
only be used once - after that, the host developed antibodies against
the viruses.

Saeidi and Wong have taken a different approach. Their work is an
example of the exciting field of synthetic biology, where scientists
tweak biology to perform tasks that their natural counterparts cannot.
Often, this involves knitting together natural components in new
combinations, like picking parts off a shelf to create custom-built
living things. In this case, Saeidi and Wong connected the genetic
components for recognising P.aeruginosa, creating pyocin and
committing explosive suicide, so that the first event would trigger
the latter two.

The field has produced some amusing parlour tricks as well as more
useful achievements, including using bacteria and fungi to make
antimalarial drugs, create biofuels, decontaminate water and even hunt
cancer cells. But until now, no one has tried to send bacteria after
their own kind. Saeidi and Wong's study may be preliminary, but they
have blazed a fresh and intriguing trail.



--
Nathan McCorkle
Rochester Institute of Technology
College of Science, Biotechnology/Bioinformatics

--
You received this message because you are subscribed to the Google Groups "DIYbio" group.
To post to this group, send email to diybio@googlegroups.com.
To unsubscribe from this group, send email to diybio+unsubscribe@googlegroups.com.
For more options, visit this group at http://groups.google.com/group/diybio?hl=en.