„BaKillus“: Engineering a microbe-hunting microbe

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 Bacillus subtilis to enable this bacterium to actively detect, swim towards, attach to, and finally kill Staphylococcus aureus with peptide antibiotics. This strategy would involve a variety of different modules and possibilities to reprogram B. subtilis. To achieve the above mentioned properties, we initially would introduce the autoinducer-peptide (AIP) sensing two-component system AgrC/AgrA of S. aureus into B. subtilis, to create a S. aureus 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 E. coli.

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