The cell division interactome of Enterococcus faecalis

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Enterococcus faecalis (Ef), a bacterium which is an antibiotic resistant "superbug", is widely distributed in nature, colonizing a variety of mammals, birds, reptiles, insects and other organisms. Ef has important societal relevance as a veterinary and human pathogen with the potential to cause serious disease and to spread serious antibiotic resistance to other bacteria. An essential component of Ef cell viability, growth and spread is its ability to divide. Cell division is a complex molecular process initiated by the formation of an FtsZ protein ring at the mid-cell site followed by a cascade of different proteins which interact to form the divisome (cell division interactome). In certain bacteria, FtsZ placement at the mid-cell is directed by proteins named MinC, MinD and MinE. Some bacteria, classified as Gram-positive (Gm+), lack MinE and instead possess a conserved protein called DivIVA. Other Gm+ bacteria, such as Ef, lack any Min proteins but retain DivIVA homologues. Thus, different proteins are used in the cell division process in different bacteria. Using Ef as a model microorganism to study Gm+ coccal cell division, we identified a new conserved protein, MLJD1, which binds DivIVA and which participates in Ef cell division. Disruption of this gene in Ef causes cell death. We also identified important amino acids and structures required for DivIVA functionality. In our present research, we will further investigate the Ef divisome/interactome through microbiological, microscopy, molecular, genetic and biochemical approaches. We will fully define the various interactions between at least 11 Ef cell division proteins, thereby developing the first high quality divisome/interactome map for Ef. We will produce novel insight regarding the basis of the DivIVAEf -MLJD1 interaction, the structure of MLJD1, and the interaction of these proteins with the full range of other cell division proteins. Research on the Ef divisome, and the novel proteins associated with it will produce critical information not only on how this important organism divides, but may identify avenues that may help us to combat this and other antibiotic resistant bacteria.