The paper cited below is available here:
http://www.pnas.org/cgi/content/full/104/27/11197
Udhay
http://blogs.zdnet.com/emergingtech/?p=628
July 10th, 2007
Bioengineered viruses kill bacteria
Synthetic biology is an emerging field which
involves the engineering of biological organisms.
One of the first applications has been developed
by a team of researchers from the MIT and Boston
University who built viruses to combat harmful
biofilms. These bacteriophages or phages
could soon be used to destroy bacterial biofilms
in hard to reach places such as the insides of
food processing machines. These phages are not
allowed for use in humans in the U.S., but they
could be approved for future phage-containing drugs for use in livestock.
How a virus destroys a biofilm
The above figure shows how an engineered virus,
T7, uses a two-pronged attack strategy to destroy
a biofilm composed of E. coli bacteria (Credit:
Timothy Lu and James Collins). This research has
been led by James Collins, professor of
biomedical engineering at Boston University, at
his Applied BioDynamics Laboratory. Hes working
with Timothy Kuan-Ta Lu on novel methods of
eliminating bacterial biofilms. In this lab,
they are modeling and building synthetic gene
networks for a variety of biotechnology and
biocomputing applications. [They] are also using
engineered gene networks to study general
principles underlying gene regulation.]
Before going further, what exactly are biofilms?
Here are the researchers answer. Biofilms have
only recently become recognized as a dominant
form of bacterial life. Biofilms are
multi-cellular communities made up of bacteria,
polysaccharides, nucleic acids, and various other
components. Bacteria living in the biofilm state
are more resistent to antibiotics and can cause
chronic infections in humans in addition to
causing substantial damage to man-made devices such as pipes and water towers.
So what exactly Lu and Collins have done? [They]
defined a modular system that allows engineers
to design phages to target specific biofilms. As
a proof of concept, they used their strategy to
engineer T7, an Escherichia coli-specific phage,
to express dispersin B (DspB), an enzyme known to
disperse a variety of biofilms. To test the
engineered T7 phage, the team cultivated E. coli
biofilms on plastic pegs. They found that their
engineered phage eliminated 99.997% of the
bacterial biofilm cells, an improvement by two
orders of magnitude over the phages nonengineered cousin.
This looks remarkably efficient, but limited to
one kind of bacteria. Not so fast, say the
researchers, who think their approach can be used
with many other bacteria. The teams modular
strategy can be thought of as a plug and play
library, says Collins. The library could contain
different phages that target different species or
strains of bacteria, each constructed using
related design principles to express different
enzymes. Creating such a library may soon be
feasible with new technologies for synthesizing genes quickly and cheaply.
This research work has been published in the
Proceedings of the National Academy of Sciences
under the name Dispersing biofilms with
engineered enzymatic bacteriophage (Vol. 104,
No. 27, Pp. 11197-11202, July 3, 2007). Here is a
link to the abstract which starts like this.
Synthetic biology involves the engineering of
biological organisms by using modular and
generalizable designs with the ultimate goal of
developing useful solutions to real-world
problems. One such problem involves bacterial
biofilms, which are crucial in the pathogenesis
of many clinically important infections and are
difficult to eradicate because they exhibit
resistance to antimicrobial treatments and
removal by host immune systems. To address this
issue, we engineered bacteriophage to express a
biofilm-degrading enzyme during infection to
simultaneously attack the bacterial cells in the
biofilm and the biofilm matrix, which is composed
of extracellular polymeric substances.
This paper has been published as an open access
article. So here are two links to the whole
article, in HTML format and in in PDF format (6
pages, 1.66 MB). The above illustration has been extracted from this article.
Sources: Elizabeth Dougherty, Harvard-MIT
Division of Health Sciences and Technology
July 6, 2007; and various websites
--
((Udhay Shankar N)) ((udhay @ pobox.com)) ((www.digeratus.com))
