Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes

Abstract

The three classes of enzymes which inactivate aminoglycosides and lead to bacterial resistance are reviewed. DNA hybridization studies have shown that different genes can encode aminoglycoside-modifying enzymes with identical resistance profiles. Comparisons of the amino acid sequences of 49 aminoglycoside-modifying enzymes have revealed new insights into the evolution and relatedness of these proteins. A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from these data and from the results of mutational analysis of several of the genes encoding aminoglycoside-modifying enzymes. Recent studies have demonstrated that aminoglycoside resistance can emerge as a result of alterations in the regulation of normally quiescent cellular genes or as a result of acquiring genes which may have originated from aminoglycoside-producing organisms or from other resistant organisms. Dissemination of these genes is aided by a variety of genetic elements including integrons, transposons, and broad-host-range plasmids. As knowledge of the molecular structure of these enzymes increases, progress can be made in our understanding of how resistance to new aminoglycosides emerges.

Genetic but No Phenotypic Associations between Biocide Tolerance and Antibiotic Resistance in Escherichia coli from German Broiler Fattening Farms

“…Different mechanisms are known to confer gentamicin resistance. Most common are enzymes modifying the drug by acetylation (aminoglycoside acetyltransferase, AAC), adenylation (adenylate aminoglycoside nucleotidyltransferase, ANT) or phosphorylation (aminoglycoside phosphotransferase, APH) [87,88]. Mutations in the ribosomal target have also been described [89], but could not be confirmed in our isolates.…”

The Taming of Nuclear Factor Erythroid-2-Related Factor-2 (Nrf2) Deglycation by Fructosamine-3-Kinase (FN3K)-Inhibitors-A Novel Strategy to Combat Cancers

“…BLAST searches demonstrated a set of proteins involved in encoding microbial sequences that share nearly 30% sequence homology with human FN3K [85]. For example, the aminoglycoside kinases in microbial species could confer bacterial antibiotic resistance, and this enzymatic protein is reported to possess 30% sequence homology with human FN3K [175][176][177]. Sequence alignment studies represented that these ketosamine kinases exhibit many conserved residues, viz., Lys41, Glu55, and Asp244 and a conserved DxxxxN motif from 227 to 232 in the FN3K-RP primary structure [176].…”

Patterns of Antimicrobial Resistance and ESBL Carriage in Enterobacteriaceae Isolates from Broiler Chicken in the West Region of Cameroon: A Cross-sectional Study

“…Elena López et al showed that cipro oxacin induced chromosomal recombinations in E coli enabled the bacterium to resist the drug 10 . However given the high association of aminoglycoside resistance to quinolone resistance, it suggests a shared rather than intrinsic mechanism such as plasmid mediated resistance but the lower overall prevalence of resistance to aminoglycosides shows a smaller contribution of this mechanism in the resistance observed 34,35 .…”