High-level resistance to trimethoprim in clinical isolates of Campylobacter jejuni by acquisition of foreign genes (dfr1 and dfr9) expressing drug-insensitive dihydrofolate reductases

The pathogenic bacterium Campylobacter jejuni has been regarded as endogeno usly resistant to trimethoprim. The genetic basis of this resistance was ch aracterized in two collections of clinical isolates of C. jejuni obtained f rom two different parts of Sweden. The majority of these isolates were foun d to carry foreign dfr genes coding for resistant variants of the dihydrofo late reductase enzyme, the target of trimethoprim. The resistance genes, fo und 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 iso lates were found to be negative for these dfr genes and showed a markedly l ower trimethoprim resistance level than the other isolates. The dfr9 and df r1 genes were located in the context of remnants of a transposon and an int egron, respectively. Two different surroundings for the dfr9 gene were char acterized. 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 chromo some could have been mediated by Tn5393. The frequent occurrence of high-le vel trimethoprim resistance in clinical isolates of C. jejuni could be rela ted to the heavy exposure of food animals to antibacterial drugs, which cou ld lead to the acquisition of foreign resistance genes in naturally transfo rmable strains of C. jejuni.