Design of peptide-derived antibiotics that block interactions between bacterial cell division proteins

Cell division in bacteria is coordinated by numerous membrane-associated proteins that assemble at the middle of a cell forming a complex called divisome. The divisome coordinates the spatial and temporal organization of cell division in a series of defined steps. An imbalance in these activities ultimately leads to cell death and thus prevents spreading of bacteria. Hence, targeting the cell division machinery is a promising way to obtain new antibiotics.

A subunit of the divisome is a protein complex, called FtsQBL, consisting of three subunits: FtsQ, FtsB and FtsL. The protein complex is among others responsible for initial divisome assembly. Previous work resulted in insights into the three-dimensional structure of the complex and revealed regions important for the interaction (and thus complex formation) of the three proteins. Based on the above mentioned structural insights Felix Paulussen and his colleagues are designing and optimizing peptide-derived antibiotics that block interactions of the proteins of the FtsQBL protein complex. The peptides bind one of the involved proteins and thus potentially prevent divisome assembly and bacterial multiplication. In the future these compounds will be tested for their biological effects.

Figure 1:A) Regular shaped E. coli bacteria. B)E.coli bacteria with defect in divisome, resulting in bacteria that can not divide properly anymore and show a different cell shape. C) Structural model of divisome subcomplex (FtsQBL protein complex) targeted by the AIMMS researchers

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 713669.

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