Team:LMU-Munich

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= „BaKillus“: Engineering a microbe-hunting microbe =
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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>.
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=Abstract=
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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 ''Bacillus subtilis'' to actively detect, attach to, and eventually kill ''Staphylococcus aureus'' and ''Streptococcus pneumoniae''.  
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Initially, we will introduce the autoinducer-sensing two-component systems of ''S. aureus'' and ''S. pneumoniae'' 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 ''B. subtilis'' 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 super bugs.
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Latest revision as of 13:38, 10 December 2014


Abstract

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 Bacillus subtilis to actively detect, attach to, and eventually kill Staphylococcus aureus and Streptococcus pneumoniae.

Initially, we will introduce the autoinducer-sensing two-component systems of S. aureus and S. pneumoniae 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 B. subtilis 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 super bugs.

Hi there!

Welcome to our Wiki! I'm BaKillus, the pathogen-hunting microbe, and I'll guide you on this tour through our project. If you want to learn more about a specific step, you can simply close the tour and come back to it anytime you like. So let's start!

What's the problem?

First of all, what am I doing here? The problem is, pathogenic bacteria all around the world are becoming more and more resistant against antimicrobial drugs. One major reason for the trend is the inappropriate use of drugs. With my BaKillus super powers, I want to reduce this misuse and thus do my part to save global health.

Sensing of pathogens

To combat the pathogenic bacteria, I simply eavesdrop on their communication. Bacteria talk with each other via quorum sensing systems, which I use to detect them and trigger my responses.

Adhesion

The more specific and effective I can use my powers, the lower the danger is of provoking new resistance development. So I catch pathogens whenever I get hold of them and stick to them until my work is done.

Killing

Talking about my work - killing pathogens is finally what I am made for. In response to quorum sensing molecules of the pathogens, I export a range of antimicrobial substances leading to dissipation of biofilms and the killing of the targeted bacteria.

Suicide switch

When the job is done and all the bad guys are finished, you don't need a super hero anymore. So after fulfilling my work I say goodbye to the world by activating my suicide switch.

Application

Of course I'm not only a fictional hero, but a very real one. In two different prototypes, I could be used for diagnosis or treatment of pathogen-caused diseases. However, there is still a whole lot of regulational and economical questions that have to be answered before.

See you!

So now you know my short story - and it is time for me to return to my fight for a safer world. Feel free to take a closer look on my super powers, the process of my development or the plans for a medical application.

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