Tet repressor-tet operator interaction

Tetracycline resistance genes are widespread among gram-negative aerobic bacteria. A large number of independent isolates have been characterized and most of them shown to belong to five different classes of determinants, named classes A to E. They are usually plasmid- or transposon-encoded and share several genetic and mechanistic features (Chopra et al., 1981; Izaki et al., 1966; Levy and McMurray, 1978; Mendez et al., 1980; Marshall et al., 1986; Levy, 1988). Resistance against the drug is achieved by an active export mechanism of tetracycline from the resistant cell. This is mediated by a membrane associated resistance protein (McMurray et al., 1980; Waters et al., 1983; Hillen and Schollmeier, 1983; Nguyen et al., 1983). The expression of this protein is inducible by subinhibitory amounts of tetracycline (Mendez et al., 1980). This regulation of expression occurs at the level of transcription. It is brought about by a repressor protein, which under non-inducing conditions represses expression of the resistance gene, as well as that of its own gene. Induction of tetracycline resistance is achieved by binding of tetracycline to the repressor, thereby inactivating the operator-binding function of the protein and allowing expression of both genes. The regulated genes termed tetA for resistance and tetR for repressor are arranged adjacent to each other with opposite polarity and share common regulatory sequences comprising at least two promotors and two operators per determinant (Beck et al., 1982; Wray et al., 1981; Jorgensen and Reznikoff, 1979; Hillen et al., 1984; Hillen et al., 1982a; Bertrand et al., 1983; Altenbuchner et al., 1983; Unger et al., 1984a; Unger et al., 1984b; Tovar et al., 1988).