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.