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PMID: 8385262 Published · ppublish English Journal Article Review

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

Microbiological reviews ·Vol. 57 ·No. 1 ·1993-03-00 ·Pages 138-63

Shaw KJ, Rather PN, Hare RS, Miller GH

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.

Related Genes
aac ant aph
MeSH Terms
Acetyltransferases/chemistry,genetics,metabolism Amino Acid Sequence Aminoglycosides Anti-Bacterial Agents/metabolism,pharmacology Bacteria/drug effects,enzymology,genetics Drug Resistance, Microbial/genetics Genes, Bacterial Molecular Sequence Data Nucleotidyltransferases/chemistry,genetics,metabolism Phosphotransferases/chemistry,genetics,metabolism Sequence Alignment Structure-Activity Relationship
Chemicals
Aminoglycosides Anti-Bacterial Agents Acetyltransferases Phosphotransferases Nucleotidyltransferases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shaw K J
Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
Rather P N
Hare R S
Miller G H
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Article Info
Journal
Microbiological reviews
Abbr.
Microbiol Rev
ISSN
0146-0749
DOI
10.1128/mr.57.1.138-163.1993
Published
1993-03-00
Pages
138-63
Language
English
Region
United States
NLM ID
7806086
PMCID
PMC372903
Subset
IM
External Links
PubMed source DOI: 10.1128/mr.57.1.138-163.1993 PMC Full Text
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