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Antimicrobial Agents and Chemotherapy, December 1998, p. 3059-3064, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

High-Level Resistance to Trimethoprim in Clinical Isolates of Campylobacter jejuni by Acquisition of Foreign Genes (dfr1 and dfr9) Expressing Drug-Insensitive Dihydrofolate Reductases

Amera Gibreel and Ola Sköld*

Division of Microbiology, Department of Pharmaceutical Biosciences, Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden

Received 12 March 1998/Returned for modification 29 May 1998/Accepted 9 September 1998

The pathogenic bacterium Campylobacter jejuni has been regarded as endogenously resistant to trimethoprim. The genetic basis of this resistance was characterized in two collections of clinical isolates of C. jejuni obtained from two different parts of Sweden. The majority of these isolates were found to carry foreign dfr genes coding for resistant variants of the dihydrofolate reductase enzyme, the target of trimethoprim. The resistance genes, found on the chromosome, were dfr1 and dfr9. In about 10% of the strains, the dfr1 and dfr9 genes occurred simultaneously. About 10% of the examined isolates were found to be negative for these dfr genes and showed a markedly lower trimethoprim resistance level than the other isolates. The dfr9 and dfr1 genes were located in the context of remnants of a transposon and an integron, respectively. Two different surroundings for the dfr9 gene were characterized. One was identical to the right-hand end of the transposon Tn5393, and in the other, the dfr9 gene was flanked by only a few nucleotides of a Tn5393 sequence. The insertion of the dfr9 gene into the C. jejuni chromosome could have been mediated by Tn5393. The frequent occurrence of high-level trimethoprim resistance in clinical isolates of C. jejuni could be related to the heavy exposure of food animals to antibacterial drugs, which could lead to the acquisition of foreign resistance genes in naturally transformable strains of C. jejuni.

* Corresponding author. Mailing address: Division of Microbiology, Department of Pharmaceutical Biosciences, P.O. Box 581, Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden. Phone: 46-18-4714500. Fax: 46-18-502790. E-mail: ola.skold{at}farmbio.uu.se.

Antimicrobial Agents and Chemotherapy, December 1998, p. 3059-3064, Vol. 42, No. 12
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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