Molecular Mechanisms of Genome Maintenance
We live now in the “Age of Bacteria.” Our planet has always been in the “Age of Bacteria,” ever since the first fossils - bacteria, of course - were entombed in rocks more than 3 billion years ago. On any possible, reasonable or fair criterion, bacteria are - and always have been - the dominant forms of life on Earth - Full House, Stephen J Gould
The world biomass of bacteria surpasses that of all animal and plant life: the estimated global number of bacterial cells is approximately two to five orders of magnitude higher than the total number of animal and plant cells. Bacteria play key roles in maintenance of the biosphere, in nutrient recycling, in human and animal health and disease, as well as in a plethora of man-made technologies. Accurate genome segregation is an essential cellular process that guarantees the stable transmission of genetic material during cytokinesis. Despite their importance, our knowledge of the mechanisms that underpin genome maintenance in bacteria is very fragmented. Low copy number plasmids - extrachromosomal episomes that are distributed widely in procaryotes - are tractable and informative elements to probe the events leading to accurate genome segregation. Specifically, by dissecting the segregation of antibiotic resistance plasmids, we aim to gain wide-ranging insights into the molecular mechanisms that underpin genome maintenance in bacteria. Additionally, the segregation apparatus has significant potential as a novel target for new antibacterial agents that are required urgently as existing antibiotics inexorably fail. We also investigate the action of toxin-antitoxin (TA) complexes that are widely distributed in bacteria, including in pathogenic species. TAs induce reversible cell cycle arrest or programmed cell death in response to starvation or other adverse conditions. As the toxin components of TAs are potential intracellular 'molecular timebombs', activation of these toxins with designer drugs may provide a novel antibiosis strategy.
Goodale A, Michailidis F, Watts R, Chok SC, Hayes F (2020) Characterization of permissive and non-permissive peptide insertion sites in chloramphenicol acetyltransferase. Microb Pathog, in press.
Caccamo M, Dobruk-Serkowska A, Rodríguez-Castañeda F, Pennica C, Barillà D, Hayes F (2020) Genome segregation by the Venus Flytrap mechanism: probing the interaction between the ParF ATPase and the ParG centromere binding protein. Front Mol Biosci 7:108.
Hayes F, Barillà D (2019) Overproduction, separation and purification of affinity-tagged proteins from Escherichia coli, p. 101-121. In Biomolecular and Bioanalytical Techniques: Theory, Methodology and Applications (Ramesh V, ed.). John Wiley & Sons Ltd.