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

Abstract

ABSTRACT 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 Tn 5393 , and in the other, the dfr9 gene was flanked by only a few nucleotides of a Tn 5393 sequence. The insertion of the dfr9 gene into the C. jejuni chromosome could have been mediated by Tn 5393 . 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.