Aminoglycoside-modifying enzyme of an antibiotic-producing bacterium acts as a determinant of antibiotic resistance in Escherichia coli.

Abstract

Plasmid-determined antibiotic resistance is widespread in clinical isolates of bacteria. Most determinants of resistance (r-determinants) have no homology with the chromosomal genes of their hosts and Watanabe (1) has suggested that rdeterminants exist "somewhere" in nature as a reservoir of chromosomal genes and that, under the appropriate selection pressures, they were "picked-up" by promiscuous sex factors and, directly or indirectly, transferred to their present hosts.It has been demonstrated (2-8) that many antibiotic-producing bacteria contain antibiotic-modifying enzymes that are related to those that determine antibiotic resistance in plasmid-containing bacteria. To date, aminoglycoside O-phosphorylating and N-acetylating enzymes (2), aminocyclitol O-phosphorylating enzymes (3-6) and chloramphenicol acetyltransferase (EC 2.3.1.28) (7, 8) have been detected in antibiotic-producing strains; these enzymes have substrate ranges similar to the plasmid-mediated enzymes found in various Gram-positive and Gram-negative bacteria. It has been suggested, therefore, that antibiotic-producing organisms might represent the origin of r-determinants (2-3).Support for this notion would come from the demonstration of protein or nucleic acid relationships between antibioticproducing organisms and plasmid-containing antibiotic-resistant bacteria. One can also ask if a gene coding for antibioticmodification in an antibiotic-producing organism could be transplanted to unrelated bacteria such as Escherichia coli; and whether or not this gene would determine antibiotic resistance in the latter.

Chromosomal aadD2 Encodes an Aminoglycoside Nucleotidyltransferase in Bacillus clausii

“…Aminoglycoside-modifying activity in the supernatant (S100) was tested by the phosphocellulose paper-binding technique with [␣-32 P]ATP (specific activity, 30 Ci/mmol) as described previously (8). Aminoglycosides (67 g/ml, i.e., 1.4 ϫ 10 Ϫ1 mM kanamycin or tobramycin) were incubated with S100 extracts at 30°C for 30 min in TMND buffer (0.06 M Tris-HCl, 0.04 M MgCl 2 , 0.4 M NH 4 Cl, 1.6 ϫ 10 Ϫ4 M dithiothreitol [pH 7.1]). Nucleotide sequence accession number.…”

“…However, aminoglycoside inactivation has rarely been reported for Bacillus spp. An aph(3Ј)-IVa gene from a butirosin-producing strain of Bacillus circulans was reported and subsequently sequenced (4,10). This gene encodes an aminoglycoside 3Ј-O-phosphotransferase type IV which confers resistance to butirosin, gentamicin B, kanamycin, lividomycin, neomycin, paromomycin, and ribostamycin by modifying these aminoglycosides at the 3Ј-hydroxyl group (10).…”

The sequence of an antibiotic resistance gene from an antibiotic‐producing bacterium

“…It has been suggested that antibiotic-producing organisms might be the primary source of clinically significant antibiotic resistance [4]. The sequences of the APH genes from the antibiotic resistance transposons, Tn5 [5] and Tn903 161, are known; also, the APH genes from B. circulans [7] and Streptomyces fradiae [S] have been cloned and shown to confer antibiotic resistance in their recipient strains. We now report the cloning and sequencing of the APH gene from B. circulans and the comparison of its translated protein sequence with those from the transposons.…”

New aminoglycoside-modifying enzymes APH(3′)-VIII and APH(3′)-IX in Acinetobacter rudis and Acinetobacter gerneri

“…20 However, in other instances, and as discussed above, a physiological role is consistent with aphA being housekeeping genes. 21 Our data confirm that resistance genes can also be found in susceptible environmental bacteria.…”