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Plasmid-mediated resistance to gentamicin in Staphylococcus aureus: the involvement of a transposon
Abstract:
Resistance to gentamicin, tobramycin and kanamycin (GmrTmrKmr) in strains of Staphylococcus aureus isolated from clinical sources in Australia is mediated by a 4.7 kb transposable element, designated Tn4001. A 2.5 kb HindIII fragment which maps symmetrically within Tn4001, and encompasses the aminoglycoside-resistance coding region, has been shown to hybridise with fragments of identical size in HindIII digests of three different GmrTmrKmr plasmids, two of which were self-transmissible, from strains of S. aureus isolated in the USA. Examination by electronmicroscopy of self-annealed molecules of the North American GmrTmrKmr plasmids revealed the presence of stem and loop structures similar to those produced by Tn4001, but with shorter inverted repeats. These results suggest that GmrTmrKmr in strains of S. aureus isolated in the USA is, or once was, transposable, and that transposable elements analogous to Tn4001 may be found in isolates of GmrTmrKmr S. aureus worldwide.
Insights
Aminoglycoside resistance in Staphylococcus aureus strains is linked to a transposable element, Tn4001. Similar elements found in US strains suggest this resistance mechanism is globally distributed in S. aureus.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Aminoglycoside antibiotics like gentamicin, tobramycin, and kanamycin are crucial for treating Staphylococcus aureus infections.
- Emerging resistance to these antibiotics poses a significant threat to public health.
- Understanding the genetic basis of this resistance is vital for developing effective treatment strategies.
Purpose of the Study:
- To investigate the genetic basis of gentamicin, tobramycin, and kanamycin resistance (GmrTmrKmr) in Staphylococcus aureus.
- To determine if the transposable element Tn4001, identified in Australian strains, is present in resistant S. aureus from other regions.
- To compare the characteristics of resistance-mediating elements in different geographical isolates.
Main Methods:
- Molecular characterization of the transposable element Tn4001 from Australian S. aureus strains.
- Hybridization assays using a specific fragment of Tn4001 against DNA from US S. aureus strains.
- Electron microscopy to examine the structural features of resistance plasmids from US strains.
Main Results:
- The transposable element Tn4001 mediates GmrTmrKmr in Australian S. aureus.
- A conserved 2.5 kb HindIII fragment within Tn4001 hybridized with similar fragments from GmrTmrKmr plasmids in US S. aureus strains.
- Electron microscopy revealed structural similarities, including stem-loop formations, between Tn4001 and resistance elements in US plasmids, suggesting potential transposable activity.
Conclusions:
- The genetic element responsible for GmrTmrKmr in S. aureus appears to be conserved across different geographical locations.
- Transposable elements analogous to Tn4001 are likely widespread in GmrTmrKmr S. aureus isolates globally.
- This suggests a common evolutionary pathway for aminoglycoside resistance in S. aureus.