Prior exposure of agriculture cephalosporin ceftiofur impaired conjugation of blaCTX-M-65 gene-bearing plasmid in Salmonella Saintpaul.

ABSTRACT

AIMS: Although a link between agricultural cephalosporin use and resistance in Salmonella has been demonstrated with the drug ceftiofur, the underlying mechanism of the correlation is unclear. This study investigated the impact of ceftiofur exposure in S. Saintpaul on ceftriaxone resistance, the gene expression and the conjugative transfer of the blaCTX-M-65 gene. METHODS AND RESULTS: Prior ceftiofur exposure caused a twofold increase in MIC from 1024 to 2048 µg ml-1 towards ceftriaxone and increased the enzymatic activity of BlaCTX-M-65 2·2 folds from 3·46 to 7·67 nmol nitrocefin hydrolysed min-1 . A threefold upregulation in gene expression of the blaCTX-M-65 gene was also observed. Donors exposed to ceftiofur subsequently demonstrated a 2·5-fold decrease in transfer efficiency. CONCLUSIONS: Prior exposure of S. Saintpaul to ceftiofur led to increased phenotypic resistance towards ceftriaxone while its ability to spread the cephalosporin resistance through conjugation, conversely, was impaired. SIGNIFICANCE AND IMPACT OF THE STUDY Findings from this study shed light on one possible mechanism in which agricultural cephalosporin exposure in Salmonella may subsequently impact clinical treatment. The finding that cephalosporin exposure in donors may hinder the subsequent spread of resistance instead of aiding it up was counter-intuitive.