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.
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.
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.
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.
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.
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.