Nuclease Colicins: Mode of Action, Immunity and Mechanism of Import into Escherichia coli
Justyna A. Wojdyla, Grigorios Papadakos and Colin Kleanthous
from: The Bacteriocins: Current Knowledge and Future Prospects (Edited by: Robert L. Dorit, Sandra M. Roy and Margaret A. Riley). Caister Academic Press, U.K. (2016) Pages: 35-64.
Abstract
Colicins were the first bacteriocins to be identified, christened by their discoverer André Gratia in 1925 when he noticed one strain of Escherichia coli producing a toxic diffusible substance that killed a neighbouring E. coli. Since then hundreds if not thousands of peptide and protein bacteriocins have been described, which are part of the diverse arsenal of natural antibacterial compounds made by Gram-negative and Gram-positive bacteria to fend off competitors. In keeping with their being the genesis of bacteriocin research, colicins remain some of the most studied and best understood particularly in terms of how bacteriocins breach the formidable defenses of bacteria. Colicins kill cells by a variety of mechanisms that fall into two cytotoxic classes; enzymatic colicins cleave either nucleic acids or peptidoglycan precursors while pore-forming colicins depolarize the cytoplasmic membrane. Extensive biochemical, structural and biophysical work has been published for both classes. Here, we review work primarily on nuclease colicins, their cytotoxicity, immunity and import, areas that have seen some of the greatest recent advances. There is now good molecular understanding of how colicin nucleases bind their specific immunity proteins and how this has underpinned the diversification of these high affinity complexes. The key molecular recognition events in which colicins engage at the cell surface, periplasm, inner membrane and cytoplasm are also well understood. Future challenges in the field include determining how nuclease colicins translocate between these cellular compartments and how much of the translocation process is energy dependent and the extent to which the toxins must be unfolded during import. Answering these questions will not only further our understanding of the colicin entry mechanism, enhancing our ability to fully exploit the biomedical and biotechnological potential of bacteriocins, but will also provide insight into the workings of the Gram-negative cell envelope itself read more ...
