Health and Synthetic Biology VI
Translation by I. A. Martínez
and J. R. Aguilar Cosme
Health and iGEM
The ingenuity of the participants of the iGEM contest of Synthetic Biology has also made interesting contributions to health care. Here we present some of the most interesting ideas, not only by considering their success in the competition – often, a team will not have the opportunity to complete the experimental phase of their project on time-, but also considering their creative qualities and contributions to the parts registry.
Bacteria, parasites and yeasts.
Bacteria
iGEM teams have used various bacterial chassis for healthcare purposes mainly as mechanisms that produce biological effectors, probiotics, biosensors and vectors.
Producers of biological effectors – Two types can be distinguished: those that produce only one type of effector and composite systems that produce more than one effector and that may have a regulatory circuit.
Among the single-product producers, we find mechanisms for quorum sensing disruption (or “quorum quenching”), which have been addressed by the team St. Andrews 2010 for infections with Vibrio cholerae; this system is similar to that published by Duan and March (2010), and is based on Cal-1 synthesis by Escherichia coli to prevent intestinal colonization by Vibrio cholerae.
The breaking of biofilms through quorum quenching in Staphylococcus aureus has been performed using the peptide inhibitor of RNAIII (RIP) by the team SDU-Denmark 2009 and HKUST 2010. Denmark’s team focused on the development of an adhesive strip, which they call “BactoBandage” and its quorum quenching system –an E. coli chassis expressing RIP- to prevent infection by S. aureus on wounds. On the other hand, the HKUST team developed a a system based on a Lactobacillus chassis that expresses RIP in the digestive tract and prevents gastroenteritis caused by S. aureus. The use of quorum quenching to treat infections has been the main topic for some revisions, such as Henzev and Givskov, (2003), Zhang and Dong, (2004) and Kalia and Purohit,(2011).
Another mechanism of intercellular communication disruption in bacterial communities is addressed by team HKUST 2011, who devised an E. coli capable of expressing the enzyme toluene-4-monooxygenase, i.e., the enzyme responsible of indole degradation in a community of pathogenic E. coli. Because indole acts as an intercellular messenger that induces a stress-response, with its disruption, the cells fail to promote a proper stress response and exhibit an enhanced antibiotic susceptibility.
The use of communication by quorum sensing as a signal to express a biological agent is a similar concept that was applied by the British Columbia 2010 team. This team developed a system based on bacteriophages that introduce the gene DspB into S. aureus -the gene encodes the protein dispersine, capable of degrading biofilms- under the control of a quorum sensing-regulated promoter; in this way, DspB will be expressed when S. aureus reaches high densities, as in the case of biofilms. This is a system similar to one previously published, Lu and Collins (2007).
Disruption of biofilms has also been addressed by the Fatih-Turkey 2011 team, who used a Bacillus subtilis chassis to express an anti-lipopolysaccharide factor (anti-LPS factor) from horseshoe crabs (Limulus polyphemus) in order to fight gram-negative bacteria. This crab, due to the absence of antibodies in invertebrates, makes use of alternative systems to fight bacterial infections, among which is the expression of antibacterial peptides, such as anti-LPS factor.
Another interesting project was developed by the METU-Gene 2009 team. They devised a system based in an E. coli chassis that expresses EGF (human epithelial growth factor) and help in wound healing, using also an adhesive band, like the aforementioned BactoBandage. Here are some related references: Buckler, et al. (1985) and Brown, et al. (1989).
In 2011, the Postdam Bioware team used an E. coli chassis to express and evolve a microviridine –a type of cyclic peptide from cyanobacteria- capable of inhibiting proteases. The team discussed possible applications for degrading clinically important proteases, such as the angiotensinogen converting enzyme or the HIV protease. A related reference is Bagchi, et al., in Satyanarayana, et al. (2012).
Translation by I. A. Martínez
and J. R. Aguilar Cosme
