Team:LMU-Munich

From 2014.igem.org

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= „BaKillus“: Engineering a microbe-hunting microbe =
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= „BaKillus“ – Engineering a pathogen-hunting microbe =
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Increasing bacterial resistance to classical antibiotics remains a serious threat and urges the development of novel pathogen-killing strategies. Exploiting bacterial communication mechanisms such as quorum sensing is a promising strategy to specifically target certain pathogens. The major aim of this project is the introduction of a genetic circuit enabling </i>Bacillus subtilis</i> to actively detect, attach to, and eventually kill </i>Staphylococcus aureus</i> and </i>Streptococcus pneumoniae</i>. Initially, we will introduce the autoinducer-sensing two-component systems of </i>S. aureus</i> and </i>S. pneumoniae</i> into <i>B. subtilis</i>.  to create a pathogen-detecting strain. By utilizing quorum sensing-dependent promoters, we will then trigger pathogen-killing strategies like the production of antimicrobial peptides or biofilm degradation. As a safety measure a delayed suicide-switch guarantees non-persistence of genetically modified </i>B. subtilis</i> in the absence of pathogens. We envision the use of BaKillus as a smart, cheap and simple-to-use medical device for diagnostics and targeted treatment of multiresistant superbugs.
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Ever increasing bacterial resistance to classical antibiotics remains a serious threat and urges the development of novel pathogen killing strategies. Exploiting bacterial communication mechanisms, like quorum sensing systems, seems to be a promising strategy for specifically killing pathogens and would allow targeting only those bacteria that use a specific autoinducer. Towards that goal, we want to introduce a genetic circuit into <i>Bacillus subtilis</i> to enable this bacterium to actively detect, swim towards, attach to, and finally kill <i>Staphylococcus aureus</i> with peptide antibiotics. This strategy would involve a variety of different modules and possibilities to reprogram <i>B. subtilis</i>. To achieve the above mentioned properties, we initially would introduce the autoinducer-peptide (AIP) sensing two-component system AgrC/AgrA of <i>S. aureus</i> into <i>B. subtilis</i>, to create a <i>S. aureus</i> detecting strain. Subsequently, downstream processes, such as  subtilin production and export, dispersin export to degrade biofilms, etc. would have to be introduced by using Agr-sensitive promoters to trigger the microbe killing mechanisms in response to an AIP gradient. Moreover, our project will also aim at expanding the “Bacillus BioBrick Box” of the 2012 iGEM-team to provide more high quality parts, including a Gram-positive quorum-sensing systems, to a research community that is still dominated by working with the Gram-negative model organism <i>E. coli</i>.
 
<html><div style="background: rgb(45, 46, 131); color: white; text-size: xx-large; float:right;"> SUCH IGEM! </div></html>
<html><div style="background: rgb(45, 46, 131); color: white; text-size: xx-large; float:right;"> SUCH IGEM! </div></html>

Revision as of 12:47, 30 August 2014

„BaKillus“ – Engineering a pathogen-hunting microbe

WOW

Doge

Increasing bacterial resistance to classical antibiotics remains a serious threat and urges the development of novel pathogen-killing strategies. Exploiting bacterial communication mechanisms such as quorum sensing is a promising strategy to specifically target certain pathogens. The major aim of this project is the introduction of a genetic circuit enabling </i>Bacillus subtilis</i> to actively detect, attach to, and eventually kill </i>Staphylococcus aureus</i> and </i>Streptococcus pneumoniae</i>. Initially, we will introduce the autoinducer-sensing two-component systems of </i>S. aureus</i> and </i>S. pneumoniae</i> into B. subtilis. to create a pathogen-detecting strain. By utilizing quorum sensing-dependent promoters, we will then trigger pathogen-killing strategies like the production of antimicrobial peptides or biofilm degradation. As a safety measure a delayed suicide-switch guarantees non-persistence of genetically modified </i>B. subtilis</i> in the absence of pathogens. We envision the use of BaKillus as a smart, cheap and simple-to-use medical device for diagnostics and targeted treatment of multiresistant superbugs.


SUCH IGEM!

panel discussion