High-level gentamicin resistance among enterococci.

The bi-functional enzyme 6'-aminoglycoside acetyltransferase (AAC-6')-2" aminoglycoside phosphotransferase (APH-2"), which is encoded by the 2 kb fused gene aacA-aphD, mediates gentamicin resistance in Enterococcus faecalis. This gene is associated with the composite transposon Tn5281 that shares extensive homology with transposons Tn4001 and Tn4031 found in staphylococci. Typically these transposons are characterized by the resistance gene being flanked by 1.35 kb insertion sequences (IS256). The resistance gene (aacA-aphD) appears identical among all E. faecalis studied, but restriction enzyme analysis indicates notable heterogeneity within the flanking regions. Various combinations of IS256-like and IS257-like elements, or portions thereof, have been described in different resistant isolates. As gentamicin resistance has been described in other enterococcal species (E. faecium, E. avium, E. gallinarum, E. raffinosus, E. casseliflavus) homology with the resistance gene of E. faecalis has largely been maintained, but more extensive variations in the flanking sequences have been noted. Although many similarities exist among enterococcal gentamicin resistance determinants, heterogeneity in the flanking regions indicates that measurable divergence exists among these determinants. This divergence may be of value in characterizing the mechanisms and natural course of gentamicin resistance dissemination which now includes staphylococci, enterococci and streptococci.