Genetic Mechanisms of Transfer of Drug Resistance

Abstract

The mobile elements responsible for capture and mobilization of resistance genes include composite transposons, characterized by insertion sequences on either side of a single gene or a small number of genes. Early examples were Tn5, Tn9, and Tn10, coding resistance to kanamycin + streptomycin, chloramphenicol, and tetracycline, respectively. Possibly any chromosomal resistance gene can become part of a composite transposon by receiving an insertion sequence on both sides. Simple or unit transposons, with only short repeats flanking the transposition genes, have also been efficient vehicles for resistance gene dissemination. Examples are Tn3 and relatives carrying a wide variety of extended-spectrum TEM-β-lactamases, and Tn1546 with its entire vancomycin resistance operon. Conjugative transposons are also important vectors of vancomycin resistance. Integrons are natural expression vectors into which resistance genes, packaged as small mobile “gene cassettes,” are inserted in tandem arrays downstream of a promoter to form resistance operons. A wide variety of cassette-borne resistance genes has been identified, most recently those encoding carbapenemases. Novel classes of antibiotics directed at new targets are needed. Although resistance will eventually emerge, the process should be slower than for new antibiotics of existing classes.