E. coli growth inhibition by exporting in the periplasm oligopeptides interfering with the divisome PPls

Antibiotic resistance issues necessitate the continued discovery and development of new antibacterial agents. By the way, as long as the targets remain the same, it is only a matter of time for antibiotic resistance to emerge. For this reason, finding new targets for antibacterial agents seems to be critical and one field that can be taken into consideration is that of PPIs inhibition. The entire divisome interaction pathway, now available for both Escherichia coli and Streptococcus pneumoniae (Maggi et al., 2008), shows that the interaction web is conserved despite the phylogenetic distance between these two organisms. The conserved and essential nature of several PPIs involved in the division process makes the inhibition of these interactions a novel and unexplored field where we can look for new targets and compounds for the development of new antibacterial drugs. In E. coli, ten out the twenty proteins involved in the divisome assembly appear to be essential to carry out the correct division process. Most of these are localized and assembled in the periplasmic region. Therefore, to inhibit the complex formations, the oligopeptides, synthetised in the cytoplasm need to be exported in the periplasmic space. To evaluate the ability of a fragment of a divisome protein domain to inhibit the cell growth when free in the periplasmic region, the sequence coding for few aminoacids, identified as involved in its interaction with divisome partners, was cloned in frame with the RR motif recognized by the Tat export pathway. The bacterial survival as well as the impairment of a particular interaction under investigation was then tested. In the poster, we report data on the bacterial growth impairment by inhibition of the divisome protein FtsQ interactions. Maggi et al., Microbiology. 2008. 154:3042-52.