[Biochemical kinetics of plasmid replication processes].

Two groups of plasmid replication reactions occurring during the growth of cell populations were kinetically characterized: 1) short-term intermediate processes coupled with changes in plasmid concentrations in host cells and occurring in the first few generations; 2) long-term processes resulting in the loss of plasmids and occurring during prolonged cultivation of cells. It was shown that first group processes are determined by the ratios of plasmid replication rates relative to cell growth. Using growing populations of E. coli as examples, it was shown that the shape of kinetic curves reflecting the plasmid copy number depends on the nature of their replicon. In this case plasmids with ColE1 replicon exhibit kinetic behaviour of the first type (temporal loss of plasmid copy number in the cells), whereas plasmids with p15 replicon display the second type behaviour consisting in the decrease of the plasmid copy number followed by its short-term drastic increase. For both types of kinetic behaviour a kinetic description adequately reflecting these processes is given. It is supposed that the loss of plasmids during long-term cultivation of cell populations may be associated with both segregation (lower growth rates of plasmid-containing cells in comparison with cells containing no plasmids) and mutation mechanisms. Kinetic descriptions of both mechanisms are proposed and principles of their discrimination are formulated. Practical recommendations for the prevention of the plasmid loss by the cells that are based on theoretical data are given.