Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm.

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Tolmasky ME

Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm.

Front Biosci. 2000 Jan 1;5:D20-9.

PubMed ID

10702385 [ View in PubMed

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Abstract

Aminoglycosides (Ags) are a group of antibiotics that exert their bactericidal activity primarily by inhibition of protein synthesis. Aminoglycoside (Ag) molecules bind to the bacterial 30S ribosomal subunit rendering the ribosomes unavailable for translation, which results in cell death. Although these antibiotics are and have been very useful to treat a variety of bacterial infections, in recent years the number of Ag resistant and multiresistant isolates has seriously increased. Mechanisms of resistance to Ag include enzymatic inactivation by acetyltransferases, nucleotidyltransferases (adenylyltransferases), and phosphotransferases, ribosomal alterations, and reduced permeability. Of all Ags, amikacin (Ak) is the most resistant to the action of Ag-modifying enzymes. However, AAC(6')-I type enzymes (a group of 6'-N-acetyltransferases) can utilize Ak as substrate and confer resistance to this antibiotic in addition to other Ags. The gene aac(6')-Ib was found in various bacterial species and various research groups performed mutagenesis studies on this or related enzymes. In one case, aac(6')-Ib was identified in a transposable element, Tn1331, included in pJHCMW1, a plasmid isolated from a clinical K. pneumoniae strain. Tn1331 includes genes encoding two Ag-modifying enzymes (aac(6')-Ib and ant(3")-Ia) and two beta-lactamases (blaTEM and blaOXA-9). Characterization of other functions of the pJHCMW1 plasmid showed the presence of an RNA-regulated replication origin and a functional oriT. Stability by multimer resolution is achieved by the Tn1331 resolvase.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amikacin	30S ribosomal protein S12	Protein	Escherichia coli (strain K12)	Yes	Inhibitor	Details