Selective amplification of genes on the R plasmid, NR1, in Proteus mirabilis: an example of the induction of selective gene amplification.

The drug-resistance plasmid, NR1, is a 37-micron circular DNA molecule that contains two components: the resistance transfer factor (29 micron) carrying the transfer genes and the genes for tetracycline resistance, and the r-determinant (8 micron) carrying the genes for resistance to several other antibiotics including chloramphenicol (Cm). In Proteus mirabilis, these two components are capable of independent replication, or they may replicate as a composite molecule. When cells of P. mirabilis containing NR1 are cultured in medium containing Cm at 250 microgram/ml a growth lag of 20-35 hr ensues. During this lag, Cm induces the selective amplification of the r-determinant, including the gene for resistance to Cm. The amplification results from the excision of the r-determinant from the R plasmid, the independent replication of the r-determinant to give polymeric as well as monomeric r-determinants, and the eventual reintegration of multiple tandem copies of the r-determinant with the resistance transfer factor to form a new R plasmid with multiple copies of the r-determinant. This mechanism represents a new level of control of gene expression in bacterial systems--namely, the induction of selective gene amplification.