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Transposon-mediated multiple antibiotic resistance in Acinetobacter strains
Abstract:
Acinetobacter calcoaceticus subsp. anitratus, which is unusually resistant to multiple antibiotics, was the cause of an epidemic of respiratory tract infections in patients in an intensive care unit. A representative isolate of the epidemic strain was found to contain the aminoglycoside-modifying enzymes 3-N-acetyltransferase, 3'-phosphotransferase, and 3"-adenylyltransferase, which confer resistance to gentamicin, kanamycin, and streptomycin, respectively. In addition, the strain produced a cephalosporinase and was resistant to penicillins due to the production of a TEM-2 beta-lactamase. The bacterial isolate also exhibited resistance to chloramphenicol, tetracycline, and sulfonamides. The resistant phenotype of this strain was similar to resistance patterns frequently observed in endemic hospital flora, suggesting that the transfer of an R plasmid into Acinetobacter sp. may have occurred. However, antibiotic resistance could not be transferred to any recipient by various mating procedures. After plasmid RP4 was transferred into an ampicillin- and kanamycin-susceptible derivative of the epidemic strain, mobilization of resistance to chloramphenicol, gentamicin, streptomycin, sulfonamides, and possibly tetracycline could be achieved. This mobilization was due to the transposition of a 16-megadalton DNA sequence from the Acinetobacter chromosome into plasmid RP4. Insertion of the transposable sequence occurred near the PstI and SmaI sites around position 22.5 on the physical map of plasmid RP4. We suggest that a plasmid resistant to multiple antibiotics was transferred from the hospital flora into Acinetobacter sp. but could not be maintained stably in this host. Instead, a multiply resistant DNA sequence was transposed and stably integrated into the Acinetobacter chromosome. The occurrence of such multiply resistant transposons on conjugative plasmids contributes greatly to the genetic variability of bacteria and may sometimes have serious epidemiological and therapeutic consequences.
Insights
Acinetobacter calcoaceticus subsp. anitratus caused a hospital outbreak due to its multi-drug resistance. A transposable DNA sequence carrying resistance genes integrated into the bacteria
Area of Science:
- Microbiology
- Molecular Biology
- Epidemiology
Background:
- An epidemic of respiratory tract infections in an intensive care unit was caused by Acinetobacter calcoaceticus subsp. anitratus.
- The epidemic strain exhibited unusual resistance to multiple antibiotics, including aminoglycosides, penicillins, cephalosporins, chloramphenicol, tetracycline, and sulfonamides.
- The resistance patterns resembled those commonly found in hospital flora, suggesting potential plasmid transfer.
Purpose of the Study:
- To investigate the genetic basis of the multi-drug resistance in the epidemic strain of Acinetobacter calcoaceticus subsp. anitratus.
- To determine the mechanism by which antibiotic resistance was acquired and maintained in this bacterial isolate.
- To understand the epidemiological implications of multi-drug resistant Acinetobacter strains in healthcare settings.
Main Methods:
- Characterization of antibiotic resistance mechanisms, including the identification of specific modifying enzymes (e.g., 3-N-acetyltransferase, TEM-2 beta-lactamase).
- Attempted transfer of antibiotic resistance via bacterial mating procedures.
- Plasmid transfer experiments using plasmid RP4 and a susceptible derivative of the epidemic strain, followed by analysis of resistance mobilization.
Main Results:
- The epidemic strain possessed multiple aminoglycoside-modifying enzymes and a TEM-2 beta-lactamase, conferring resistance to gentamicin, kanamycin, streptomycin, and penicillins.
- While direct plasmid transfer was unsuccessful, mobilization of resistance markers (chloramphenicol, gentamicin, streptomycin, sulfonamides, tetracycline) occurred after introducing plasmid RP4.
- This mobilization was attributed to the transposition of a 16-megadalton DNA sequence from the Acinetobacter chromosome into plasmid RP4, near specific restriction sites.
Conclusions:
- A multi-drug resistant plasmid likely transferred into Acinetobacter sp. from hospital flora but was not stably maintained.
- Instead, a multiply resistant DNA sequence (transposon) integrated into the Acinetobacter chromosome, conferring stable resistance.
- The integration of such transposons contributes to bacterial genetic variability and can have significant epidemiological and therapeutic consequences.