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Variation and modeling of the probability of plasmid loss as a function of growth rate of plasmid‐bearing cells of Escherichia coli during continuous cultures

1993; Wiley; Volume: 41; Issue: 4 Linguagem: Inglês

10.1002/bit.260410402

1097-0290

Ridha Mosrati, Nabil Nancib, Joseph Boudrant,

Bacterial Genetics and Biotechnology

Abstract A large number of models concerning cultures of genetically engineered bacteria have been described. Among them, some are specifically adapted to continuous cultures and lead to the determination of two variables: (i) the difference in the specific growth rates between plasmid‐carrying cell and plasmid‐free cells (δμ) and (ii) the frequency of plasmid loss by plasmid‐containing cells (p r μ + ). Until now, studies have been performed on the global expression p r μ + and δμ, whose value during continuous assays have been supposed approximately constant (mean value) and not on separate values of both terms p r and μ + , respectively, probability of plasmid loss and specific growth rate of the plasmid‐carrying cells. So far these studies do not allow examination of the relationship between these two last parameters. Experimental results were obtained with Escherichia coli C600 galk (GAPDH), a genetically engineered strain that synthetizes an elevated quantity of glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH). From data obtained during continuous cultures, it is shown that during an assay, δμ, and p r μ + do not remain constant. An appropriate mathematical analysis of the expression of μ − (specific growth rate of the plasmid‐free cells) and μ + has been built up. This allows the evaluation of the values of μ + and μ − during the continuous cultures carried out at different dilution rates. Values of p r have been calculated from these data. Indeed our results show that p r increases with μ + . A modeling approach which allows correct simulation of this variation is also proposed. This model is derived from the Hill equation regarding cooperative binding of enzymic type reaction. © 1993 John Wiley & Sons, Inc.